How different neural crest derivatives differentiate in distinct embryonic locations in the vertebrate embryo is an intriguing issue. Many attempts have been made to understand the underlying mechanism of specific pathway choices made by migrating neural crest cells. In this speculative review we suggest a new mechanism for the regulation of neural crest cell migration patterns in avian and mammalian embryos, based on recent progress in understanding the expression and activity of receptor tyrosine kinases (...) during embryogenesis. Distinct subpopulations of crest‐derived cells express specific receptor tyrosine kinases while residing in a migration staging area. We postulate that the differential expression of receptor tyrosine kinases by specific subpopulations of neural crest cells allows them to respond to localized growth factor ligand activity in the embryo. Thus, the migration pathway taken by neural crest subpopulations is determined by their receptor tyrosine kinase response to the differential localization of their cognate ligand. (shrink)

Neural crest cells are remarkable in their extensive and stereotypic patterns of migration. The pathways of neural crest migration have been documented by cell marking techniques, including interspecific neural tube grafts, immunocytochemistry and Dil‐labelling. In the trunk, neural crest cells migrate dorsally under the skin or ventrally through the somites, where they move in a segmental fashion through the rostral half of each sclerotome. The segmental migration of neural crest cells appears (...) to be prescribed by the somites, perhaps by an inhibitory cue from the caudal half. Within the rostral sclerotome, neural crest cells fill the available space except for a region around the notochord, suggesting the notochord may inhibit neural crest cells in its vicinity. In the cranial region, antibody perturbation experiments suggest that multiple cell‐matrix interactions are required for proper in vivo migration of neural crest cells. Neural crest cells utilize integrin receptors to bind to a number of extracellular matrix molecules. Substrate selective inhibition of neural crest cell attachment in vitro by integrin antibodies and antisense oligonucleotides has demonstrated that they possess at least three integrins, one being an α1β1 integrin which functions in the absence of divalent cations. Thus, neural crest cells utilize complex sets of interactions which may differ at different axial levels. (shrink)

Two embryonic tissues—the neural crest and the cranial placodes—give rise to most evolutionary novelties of the vertebrate head. These two tissues develop similarly in several respects: they originate from ectoderm at the neural plate border, give rise to migratory cells and develop into multiple cell fates including sensory neurons. These similarities, and the joint appearance of both tissues in the vertebrate lineage, may point to a common evolutionary origin of neural crest and placodes from a (...) specialized population of neural plate border cells. However, a review of the developmental mechanisms underlying the induction, specification, migration and cytodifferentiation of neural crest and placodes reveals fundamental differences between the tissues. Taken together with insights from recent studies in tunicates and amphioxus, this suggests that neural crest and placodes have an independent evolutionary origin and that they evolved from the neural and non‐neural side of the neural plate border, respectively. BioEssays 30:659–672, 2008. © 2008 Wiley Periodicals, Inc. (shrink)

Neural crest cells are multipotent progenitors, capable of producing diverse cell types upon differentiation. Recent studies have identified significant heterogeneity in both the fates produced and genes expressed by different premigratory crest cells. While these cells may be specified toward particular fates prior to migration, transplant studies show that some may still be capable of respecification at this time. Here we summarize evidence that extracellular signals in the local environment may act to specify premigratory crest and (...) thus generate diversity in the population. Three main classes of signals–Wnts, BMP2/BMP4 and TGFβ1,2,3–have been shown to directly influence the production of particular neural crest cell fates, and all are expressed near the premigratory crest. This system may therefore provide a good model for integration of multiple signaling pathways during embryonic cell fate specification. BioEssays 22:708–716, 2000. © 2000 John Wiley & Sons, Inc. (shrink)

Recent work has shown that segmentation underlies the patterning of the vertebrate hindbrain and its neural crest derivatives. Several genes have been identified with segment‐restricted expression, and evidence is now emerging regarding their function and regulatory relationships. The expression patterns of Hox genes and the phenotype of null mutants indicate roles in specifying segment identity. A zinc finger gene Krox‐20 is a segment‐specific regulator of Hox expression, and it seems probable that retinoic acid receptors also regulate Hox genes (...) in the hindbrain. The receptor tyrosine kinase gene Sek may mediate cell‐cell interactions that lead to segmentation. These studies provide a starting point for understanding the molecular basis of segmental patterning in the hindbrain. (shrink)

The neural crest is a transient population of multipotent progenitors arising at the lateral edge of the neural plate in vertebrate embryos. After delamination and migration from the neuroepithelium, these cells contribute to a diverse array of tissues including neurons, smooth muscle, craniofacial cartilage, bone cells, endocrine cells and pigment cells. Considerable progress in recent years has furthered our understanding at a molecular level of how this important group of cells is generated and how they are assigned (...) to specific lineages. Here we review a number of recent studies supporting a role for Wnt signaling in neural crest induction, differentiation, and apoptosis. We also summarize the timing of expression of a number of Wnt ligands and receptors with respect to neural crest induction. BioEssays 25:317–325, 2003. © 2003 Wiley Periodicals, Inc. (shrink)

Neural crest cells are multipotent progenitors, capable of producing diverse cell types upon differentiation. Recent studies have identified significant heterogeneity in both the fates produced and genes expressed by different premigratory crest cells. While these cells may be specified toward particular fates prior to migration, transplant studies show that some may still be capable of respecification at this time. Here we summarize evidence that extracellular signals in the local environment may act to specify premigratory crest and (...) thus generate diversity in the population. Three main classes of signals–Wnts, BMP2/BMP4 and TGFβ1,2,3–have been shown to directly influence the production of particular neural crest cell fates, and all are expressed near the premigratory crest. This system may therefore provide a good model for integration of multiple signaling pathways during embryonic cell fate specification. BioEssays 22:708–716, 2000. © 2000 John Wiley & Sons, Inc. (shrink)

Many of the features that distinguish the vertebrates from other chordates are derived from the neural crest, and it has long been argued that the emergence of this multipotent embryonic population was a key innovation underpinning vertebrate evolution. More recently, however, a number of studies have suggested that the evolution of the neural crest was less sudden than previously believed. This has exposed the fact that neural crest, as evidenced by its repertoire of derivative (...) cell types, has evolved through vertebrate evolution. In this light, attempts to derive a typological definition of neural crest, in terms of molecular signatures or networks, are unfounded. We propose a less restrictive, embryological definition of this cell type that facilitates, rather than precludes, investigating the evolution of neural crest. While the evolutionary origin of neural crest has attracted much attention, its subsequent evolution has received almost no attention and yet it is more readily open to experimental investigation and has greater relevance to understanding vertebrate evolution. Finally, we provide a brief outline of how the evolutionary emergence of neural crest potentiality may have proceeded, and how it may be investigated. BioEssays 30:530–541, 2008. © 2008 Wiley Periodicals, Inc. (shrink)

For both vertebrate developmental and evolutionary biologists, and also for clinicians, the neural crest (NC) is a fundamental cell population. An understanding of Sox10 function in NC development is of particular significance since Sox10 mutations underlie several neurocristopathies. Surprisingly, experiments in different model organisms aimed at identifying Sox10's role(s) have suggested at least four distinct functions. Sox10 may be critical for formation of neural crest cells (NCCs), maintaining multipotency of crest cells, specification of derivative cell (...) fates from these cells and their differentiation. Here, I discuss this controversy and argue that these functions are, in part, molecularly interrelated. BioEssays 28: 788–798, 2006. © 2006 Wiley Periodicals, Inc. (shrink)

Modularity has become a central and remarkably useful concept in evolutionary developmental biology, offering an explanation of how independent, interacting units make possible developmental events and evolutionary changes. These modules exist at several different levels of organization, from genes to signal transduction pathways to cell populations. Cell populations, which are multicellular modules, provide an opportunity both to clarify our notion of modularity and to reexamine such central concepts as cell-to-cell communication. Rosine Chandebois’s work on “cell sociology” is reframed in the (...) language of modularity in order to show how groups of cells maintain their collective identity during development and how signaling information from the group’s environment is received by the constituent cells. In a “test case” for our account of multicellular modules, we consider the vertebrate neural crest, a migratory cell population made up of several subpopulations. The neural crest proves yet again to be a complex case, showing the importance of taking into account both developmental and evolutionary transformations of multicellular modules. (shrink)

The now classical idea that programmed cell death contributes to a plethora of developmental processes still has lost nothing of its impact. It is, therefore, important to establish effective three-dimensional reconstruction as well as simulation techniques to decipher the exact patterns and functions of such apoptotic events. The present study focuses on the question whether and how apoptosis promotes neurulation-associated processes in the spinal cord of Tupaia belangeri. Our 3D reconstructions demonstrate that at least two craniocaudal waves of apoptosis consecutively (...) pass through the dorsal spinal cord. The first wave appears to be involved in neural fold fusion and/or in selection processes among premigratory neural crest cells. The second one seems to assist in establishing the dorsal signaling center known as the roof plate. In the hindbrain, in contrast, apoptosis among premigratory neural crest cells progresses craniocaudally but discontinuously, in a segment-specific manner. Unlike apoptosis in the spinal cord, these segment-specific apoptotic events, however, precede later ones that seemingly support neural fold fusion and/or postfusion remodeling. Arguing with Whitehead that biological patterns and rhythms differ in that biological rhythms depend “upon the differences involved in each exhibition of the pattern” we show that 3D reconstruction and simulation techniques can contribute to distinguish between patterns and rhythms of apoptosis. By deciphering novel patterns and rhythms of developmental apoptosis, our reconstructions help to reconcile seemingly inconsistent earlier findings in chick and mouse embryos, and to create rules for computer simulations. (shrink)

The ideas Darwin published in On the Origin of Species and The Descent of Man in the nineteenth century continue to have a major impact on our current understanding of the world in which we live and the place that humans occupy in it. Darwin’s theories constitute the core of the contemporary life sciences, and elicit enduring fascination as a potentially unifying basis for various branches of biology and the biomedical sciences. They can be used to understand the biological ground (...) of human cognition, common behavioral patterns and disorders, and psychopathology more generally in psychology, psychiatry, and neuroscience. Perhaps the best known expression of this fact is Dobzhansky’s famous dictum that “nothing in biology makes sense except in the light of evolution” (Dobzhansky T. Am Zool 4:443–452, 1964: 449; Am Biol Teach 35:125–129, 1973: 125), and given that all human behavior supervenes on some biological basis, evolutionary thinking has a vast scope even just in this regard. (shrink)

This volume aims to clarify the epistemic potential of applying evolutionary thinking outside biology, and provides a survey of the current state of the art in research on relevant topics in the life sciences, the philosophy of science, and the various areas of evolutionary research outside the life sciences. By bringing together chapters by evolutionary biologists, systematic biologists, philosophers of biology, philosophers of social science, complex systems modelers, psychologists, anthropologists, economists, linguists, historians, and educators, the volume examines evolutionary thinking within (...) and outside the life sciences from a multidisciplinary perspective. While the chapters written by biologists and philosophers of science address theoretical aspects of the guiding questions and aims of the volume, the chapters written by researchers from the other areas approach them from the perspective of applying evolutionary thinking to non-biological phenomena. Taken together, the chapters in this volume do not only show how evolutionary thinking can be fruitfully applied in various areas of investigation, but also highlight numerous open problems, unanswered questions, and issues on which more clarity is needed. As such, the volume can serve as a starting point for future research on the application of evolutionary thinking across disciplines. (shrink)

This paper offers an overview of "the species problem", arguing for a view of species as homeostatic property cluster kinds, positioning the resulting form of realism about species as an alternative to the claim that species are individuals and pluralistic views of species. It draws on taxonomic practice in the neurosciences, especially of neural crest cells and retinal ganglion cells, to motivate both the rejection of the species-as-individuals thesis and species pluralism.

Language evolution resulted from changes in our biology, behavior, and culture. One source of these changes might be human self-domestication. Williams syndrome (WS) is a clinical condition with a clearly defined genetic basis and resulting in a distinctive behavioral and cognitive profile, including enhanced sociability. In this paper we show evidence that the WS phenotype can be satisfactorily construed as a hyper-domesticated human phenotype, plausibly resulting from the effect of the WS hemydeletion on selected candidates for domestication and neural (...) crest function. Specifically, we show that genes involved in animal domestication and neural crest development and function are significantly dysregulated in the blood of subjects with WS. We also discuss the consequences of this link between domestication and WS for our current understanding of language evolution. (shrink)

Essentially we show recent data to shed new light on the thorny controversy of how teeth arose in evolution. Essentially we show (a) how teeth can form equally from any epithelium, be it endoderm, ectoderm or a combination of the two and (b) that the gene expression programs of oral versus pharyngeal teeth are remarkably similar. Classic theories suggest that (i) skin denticles evolved first and odontode‐inductive surface ectoderm merged inside the oral cavity to form teeth (the ‘outside‐in’ hypothesis) or (...) that (ii) patterned odontodes evolved first from endoderm deep inside the pharyngeal cavity (the ‘inside‐out’ hypothesis). We propose a new perspective that views odontodes as structures sharing a deep molecular homology, united by sets of co‐expressed genes defining a competent thickened epithelium and a collaborative neural crest‐derived ectomesenchyme. Simply put, odontodes develop ‘inside and out’, wherever and whenever these co‐expressed gene sets signal to one another. Our perspective complements the classic theories and highlights an agenda for specific experimental manipulations in model and non‐model organisms. (shrink)

This paper aims to explore a potential connection between two hypotheses recently put forward in the context of language evolution. One hypothesis argues that some human-specific change in the hominin brain developmental program habilitated the neuronal workspace that enabled “cognitive modernity” to unfold, also resulting in our globularized braincase. The other argues that the cultural niche resulting from our self-domestication favored the emergence of natural languages. In this article we document numerous links between the genetic changes we have claimed may (...) have brought about globularization and neural crest cells, which have been claimed to explain the constellation of distinctive traits found in all domesticated mammals. If these links turn out to be as robust as we think they are, globularization and self-domestication may well be closely related phenomena in the context of human evolution. (shrink)

Skin pigment pattern formation is a paradigmatic example of pattern formation. In zebrafish, the adult body stripes are generated by coordinated rearrangement of three distinct pigment cell‐types, black melanocytes, shiny iridophores and yellow xanthophores. A stem cell origin of melanocytes and iridophores has been proposed although the potency of those stem cells has remained unclear. Xanthophores, however, seemed to originate predominantly from proliferation of embryonic xanthophores. Now, data from Singh et al. shows that all three cell‐types derive from shared stem (...) cells, and that these cells generate peripheral neural cell‐types too. Furthermore, clonal compositions are best explained by a progressive fate restriction model generating the individual cell‐types. The numbers of adult pigment stem cells associated with the dorsal root ganglia remain low, but progenitor numbers increase significantly during larval development up to metamorphosis, likely via production of partially restricted progenitors on the spinal nerves. (shrink)

The embryonic vertebrate face is composed of similarly sized buds of neural crest‐derived mesenchyme encased in epithelium. These buds or facial prominences grow and fuse together to give the postnatal morphology characteristic of each species. Here we review the role of neural crest cells and foregut endoderm in differentiating facial features. We relate the developing facial prominences to the skeletal structure of the face and review the signals and genes that have been shown to play an (...) important role in facial morphogenesis. We also examine two experiments one at the genetic level and one at the signal level in which transformation of facial prominences and subsequent change of jaw identity was induced. We propose that signals such as retinoids and BMPs and downstream transcription factors such as Distal‐less related genes specify jaw identity. BioEssays 25:554–568, 2003. © 2003 Wiley Periodicals, Inc. (shrink)

We consider the evidence that RA†, the vitamin A metabolite, is involved in three fundamental aspects of the development of the CNS: (1) the stimulation of axon outgrowth in particular neuronal sub‐types; (2) the migration of the neural crest; and (3) the specification of rostrocaudal position in the developing CNS (forebrain, midbrain, hindbrain, spinal cord). The evidence we discuss involves RA‐induction of neurites in cell cultures and explants of neural tissue; the teratological effects of RA on the (...) embryo's nervous system; the observation that RA can be detected endogenously in the spinal cord; and the fact that the receptors and binding proteins for RA are expressed in precise domains and neuronal cell types within the nervous system. (shrink)

Recent advances in molecular biology and microanatomy have supported homologies of body parts between vertebrates and extant invertebrate chordates, thus providing insights into the body plan of the proximate ancestor of the vertebrates. For example, this ancestor probably had a relatively complex brain and a precursor of definitive neural crest. Additional insights into early vertebrate evolution have come from recent discoveries of Lower Cambrian soft body fossils of Haikouichthys and Myllokunmingia (almost certainly vertebrates, possibly related to modern lampreys) (...) and Yunnanozoon and Haikouella (evidently stem-group vertebrates). The earliest vertebrates had an unequivocally marine origin, probably evolved mineralised pharyngeal denticles before the dermal skeleton, and evidently utilised elastic recoil of the visceral arch skeleton for suction feeding. Moreover, the new data emphasise that the advent of definitive neural crest was supremely important for the evolutionary origin of the vertebrates. BioEssays 23:142–151, 2001. © 2001 John Wiley & Sons, Inc. (shrink)

Colonial ascidians offer opportunities to investigate how developmental events are integrated to generate the animal form, since they can develop similar individuals (oozooids from eggs, blastozooids from pluripotent somatic cells) through very different reproductive processes, i.e. embryogenesis and blastogenesis. Moreover, thanks to their key phylogenetic position, they can help in the understanding of the molecular mechanisms of morphogenesis and their evolution in chordates. We review organogenesis of the ascidian neural complex comparing embryos and buds in terms of topology, developmental (...) mechanisms and terminology. We propose a new interpretation of bud territories, and reconsider nervous system development based on recent results suggesting that ascidians have vertebrate placodal and neural‐crest‐like cells. Comparing embryonic and blastogenic development in Botryllus schlosseri, we propose that the bud has territories with a placodal potentiality, suggesting that chordate ancestors possessed neurogenic placodes, and that the genetic pathways regulating neurogenic placode formation were co‐opted for new developmental processes, such as blastogenesis. BioEssays 28: 902–912, 2006. © 2006 Wiley periodicals, Inc. (shrink)

Amphibians that undergo a metamorphosis provide an unparalleled opportunity to investigate how skeletal shape is generated, preserved, and transformed in development. Their pharyngeal arch (PA) cartilages, which support breathing and feeding behaviors, form embryonically from cranial neural crest cells, grow isometrically at larval stages, and abruptly change shape during metamorphosis. Further, the shape changes occur in three different ways: some adult cartilages form de novo, others emerge from within resorbing larval cartilages and some larval cartilages reshape themselves at (...) the cellular level. Isometric growth followed by abrupt shape change is unique to amphibian PA cartilages, which suggests that the origin and evolution of amphibian metamorphosis has been influenced by the tissue properties of cartilage. This essay reviews the functional role of the PA skeleton in frogs and salamanders and presents a mechanistic framework for understanding how its shape is generated, preserved, and transformed at the levels of cell behavior and specification mechanisms. (shrink)

Every cartilage and bone in the vertebrate skeleton has a precise shape and position. The head skeleton develops in the embryo from the neural crest, which emigrates from the neural ectoderm and forms the skull and pharyngeal arches. Recent genetic data from mice and zebrafish suggest that cells in the pharyngeal segments are specified by positional information in at least two dimensions, Hox genes along the anterior‐posterior axis and other homeobox genes along the dorsal‐ventral axis within a (...) segment. Many zebrafish and human mutant phenotypes indicate that additional genes are required for the development of groups of adjacent pharyngeal arches and for patterning along the mediolateral axis of the skull. The complementary genetic approaches in humans, mice and fish reveal networks of genes that specify the complex morphology of the head skeleton along a relatively simple set of coordinates. (shrink)

A flurry of technological advances in molecular, cellular and developmental biology during the past decade has provided a clearer understanding of mechanisms underlying phenotypic diversification. Building upon such momentum, a recent paper tackles one of the foremost topics in evolution, that is the origin of species‐specific beak morphology in Darwin's finches.1 Previous work involving both domesticated and wild birds implicated a well‐known signaling pathway (i.e. bone morphogenetic proteins) and one population of progenitor cells in particular (i.e. cranial neural (...) class='Hi'>crest), as primary factors for establishing beak size and shape. But these results were limited in their ability to explain fully the morphogenetic bases of patterned outgrowth. So in a quest to identify novel genes whose expression correlated with differences in beak anatomy among Darwin's finches, a DNA microarray approach was undertaken using tissues harvested from the Galápagos Islands. The results are striking and point to a protein called calmodulin, which is a mediator of cellular calcium signaling, as a key determinant of beak length. BioEssays 29: 1–6, 2007. © 2006 Wiley Periodicals, Inc. (shrink)

A wide range of anatomical features are shared by all vertebrates, but absent in our closest invertebrate relatives. The origin of vertebrate embryogenesis must have involved the evolution of new regulatory pathways to control the development of new features, but how did this occur? Mutations affecting regulatory genes, including those containing homeobox sequences, may have been important: for example, perhaps gene duplications allowed recruitment of genes to new roles. Here I ask whether comparative data on the genomic organization and expression (...) patterns of homeobox genes support this hypothesis. I propose a model in which duplications of particular homeobox genes, followed by the acquisition of gene‐specific secondary expression domains, allowed the evolution of the neural crest, extensive organogenesis and craniofacial morphogenesis. Specific details of the model are amenable to testing by extension of this comparative approach to molecular embryology. (shrink)

The phylogenetic position of the hagfish remains enigmatic. In contrast to molecular data that suggest monophyly of the cyclostomes, several morphological features imply a more ancestral state of this animal compared with the lampreys. To resolve this question requires an understanding of the embryology of the hagfish, especially of the neural crest. The early development of the hagfish has long remained a mystery. We collected a shallow‐water‐dwelling hagfish, Eptatretus burgeri, set up an aquarium tank designed to resemble its (...) habitat, and successfully obtained several embryos. By observing the histology and expression of genes known to play fundamental roles in the neural crest, we found that the hagfish crest develops as delaminating migratory cells, as in other vertebrates. We conclude that the delaminating neural crest is a vertebrate synapomorphy that seems to have appeared from the beginning of their evolutionary history, before the splitting away of the hagfish lineage. BioEssays 30:167–172, 2008. © 2008 Wiley Periodicals, Inc. (shrink)

During development of the anterior eye segment, cells that originate from the surface epithelium or the neuroepithelium need to interact with mesenchymal cells, which predominantly originate from the neural crest. Failures of proper interaction result in a complex of developmental disorders such Peters' anomaly, Axenfeld–Rieger's syndrome or aniridia. Here we review the role of transcription factors that have been identified to be involved in the coordination of anterior eye development. Among these factors is PAX6, which is active in (...) both epithelial and mesenchymal cells during ocular development, albeit at different doses and times. We propose that PAX6 is a key element that synchronizes the complex interaction of cell types of different origin, which are all needed for proper morphogenesis of the anterior eye. We discuss several molecular mechanisms that might explain the effects of haploinsufficiency of PAX6 and other transcription factors, and the broad variation of the resulting phenotypes. BioEssays 26:374–386, 2004. © 2004 Wiley Periodicals, Inc. (shrink)

Hagfishes have long held a key place in discussions of early vertebrate evolution. Frustratingly, one basis for such discussions—namely hagfish embryology—is very incompletely known, because the embryos of these animals are notoriously difficult to obtain.1,2 Fortunately, a recent publication on a Far Eastern hagfish3 describes a workable procedure for obtaining embryos and then uses this precious material to show that the hagfish neural crest arises by cell delamination as in other vertebrates—and not by epithelial outpouchings from the wall (...) of the neural tube as previously claimed.4 Importantly, because hagfish embryos should now be available on a regular basis, the way is open for additional morphological and developmental genetic investigations to help evaluate existing evolutionary scenarios and perhaps suggest new ones. BioEssays 29:833–836, 2007. © 2007 Wiley Periodicals, Inc. (shrink)

Retinoic acid (RA), a derivative of vitamin A, is essential for normal mammalian development. Developmental abnormalities induced by RA excess and vitamin A deficiency are different even though they affect the same organ systems, and it is clear that there are intraembryonic tissue differences in the requirement for RA. The developmental functions of RA are mediated by its effects on gene expression. In the nucleus, two different forms of RA bind to and activate two families of nuclear receptors, which themselves (...) co‐operate in initiating the transcription of target genes. In this article I propose that the amount of RA reaching the nucleus in different embryonic tissues is modulated by a mechanism involving three cytoplasmic binding proteins for retinol (CRBP I) and retinoic acid (CRABP I and II). Abnormalities of craniofacial development resulting from exposure of early neural plate stage embryos to RA excess have been studied in some detail; their initial stages involve alteration of both morphological development and the segment‐specific pattern of gene expression in the early hindbrain and its derived neural crest. This system is ideal for studying the relationships between retinoic acid receptors, retinoid binding proteins, and the development of genetic and morphological pattern. (shrink)

Hirschsprung disease and the multiple endocrine neoplasia type 2 syndromes are hereditary disorders related to the abnormal migration, proliferation or survival of neural crest cells and their derivatives. Hirschsprung disease is a frequent disorder of the enteric nervous system, resulting in intestinal obstruction. The multiple endocrine neoplasia type 2 syndromes predispose to cancers of neural crest derivatives. Both diseases are associated with heterozygous mutations in the RET proto‐oncogene. RET encodes a transmembrane receptor tyrosine kinase expressed in (...) neural crest lineages and whose ligand, glial‐cell‐line‐derived neurotrophic factor, has been very recently identified. In vitro expression studies demonstrate that while Hirschsprung disease mutations result in loss of function of the mutant RET tyrosine kinase, multiple endocrine neoplasia type 2 mutations lead to its constitutive activation. Thus, the two ‘faces’ of RET, gain of function and loss of function, each lead to a different syndrome, respectively: multiple endocrine neoplasia type 2, a cancer syndrome, or Hirschsprung disease, a developmental defect. (shrink)

One argument for the moving spotlight theory is that it better explains certain aspects of our temporal phenomenology than does any static theory of time. Call this the argument from passage phenomenology. In this paper it is argued that insofar as moving spotlight theorists take this to be a sound argument they ought embrace a new version of the moving spotlight theory according to which the moving spotlight is a cresting wave of causal efficacy. On this view it is more (...) than just presentness that is temporary: a range of other fundamental properties are also temporary because presentness synchronically changes the fundamental properties that are instantiated in the present moment, from those instantiated when that moment is future, or past. On this view having experiences as of presentness co-varies with the presence of presentness, allowing the moving spotlight theorist to provide a compelling explanation for why we have the temporal phenomenology we do, and to explain how we can know that we are present by reflecting on the nature of said phenomenology. (shrink)

In this chapter, we discuss a selection of current views of the neural correlates of consciousness (NCC). We focus on the different predictions they make, in particular with respect to the role of prefrontal cortex (PFC) during visual experiences, which is an area of critical interest and some source of contention. Our discussion of these views focuses on the level of functional anatomy, rather than at the neuronal circuitry level. We take this approach because we currently understand more about (...) experimental evidence at this coarse level and because these results are appropriate for arbitrating between current theoretical frameworks. We discuss the Two-Visual-Systems Hypothesis (Milner & Goodale 1995; 2006), Local Recurrency (Lamme 2010; Lamme 2006), Higher Order (Lau 2008; Lau & Rosenthal 2011) and Global Workspace theories (Baars 1997; Baars 2005; Dehaene & Naccache 2001; Dehaene 2014). Despite the apparent stark differences between conscious and unconscious perceptual processing, available evidence suggests that their neural substrates must be largely shared. This indicates that the difference in neural activity between conscious and unconscious perceptual processing is likely to be subtle and highly specialized. We argue that current experimental evidence about the involvement of specific activity in prefrontal cortex supports the higher order neural theory of consciousness. In consequence, imaging techniques that focus only on marked differences between conscious and unconscious level of activity are likely to be insensitive to the relevant neural activity patterns that underlie conscious experiences. Finally, it follows from the evidence we discuss that the functional advantages of conscious over unconscious perceptual processing may be more limited than commonly thought. (shrink)

Can findings from psychology and cognitive neuroscience about the neural mechanisms involved in decision-making can tell us anything useful about the commonly-understood mental phenomenon of making voluntary choices? Two philosophical objections are considered. First, that the neural data is subpersonal, and so cannot enter into illuminating explanations of personal level phenomena like voluntary action. Secondly, that mental properties are multiply realized in the brain in such a way as to make them insusceptible to neuroscientific study. The paper argues (...) that both objections would be weakened by the discovery of empirical generalisations connecting subpersonal properties with the personal level. It gives three case studies that furnish evidence to that effect. It argues that the existence of such interrelations are consistent with a plausible construal of the personal-subpersonal distinction. Furthermore, there is no reason to suppose that the notion subpersonal representation relied on in cognitive neuroscience illicitly imports personal-level phenomena like consciousness or normativity, or is otherwise explanatorily problematic. (shrink)

In this paper an Artificial Neural Network (ANN) model was used to help cars dealers recognize the many characteristics of cars, including manufacturers, their location and classification of cars according to several categories including: Make, Model, Type, Origin, DriveTrain, MSRP, Invoice, EngineSize, Cylinders, Horsepower, MPG_Highway, Weight, Wheelbase, Length. ANN was used in prediction of the number of miles per gallon when the car is driven in the city(MPG_City). The results showed that ANN model was able to predict MPG_City with (...) 97.50 % accuracy. The factor of DriveTrain has the most influence on MPG_City evaluation. Similar studies can be carried out for the evaluation of other characteristics of cars. (shrink)

Human neural organoid research is advancing rapidly. As Greely notes in the target article, this progress presents an “onrushing ethical dilemma.” We can’t rule out the possibility that suff...

One of the most important recent developments in the study of concepts has been the resurgence of interest in nativist accounts of the human conceptual system. However, many theorists suppose that a key feature of neural organization—the brain’s plasticity—undermines the nativist approach to concept acquisition. We argue that, on the contrary, not only does the brain’s plasticity fail to undermine concept nativism, but a detailed examination of the neurological evidence actually provides powerful support for concept nativism.

Why is neural activity in a particular area expressed as experience of red rather than green, or as visual experience rather than auditory? Indeed, why does it have any conscious expression at all? These familiar questions indicate the explanatory gap between neural activity and ‘what it’s like’-- qualities of conscious experience. The comparative explanatory gaps, intermodal and intramodal, can be separated from the absolute explanatory gap and associated zombie issues--why does neural activity have any conscious expression at (...) all?. Here I focus on comparative gaps: why is neural activity in a given area expressed as this type of experience rather than that type of experience? (shrink)

In "Brainshy: Non-neural theories of conscious experience," (this volume) Patricia Churchland considers three "non-neural" approaches to the puzzle of consciousness: 1) Chalmers' fundamental information, 2) Searle's "intrinsic" property of brain, and 3) Penrose-Hameroff quantum phenomena in microtubules. In rejecting these ideas, Churchland flies the flag of "neuralism." She claims that conscious experience will be totally and completely explained by the dynamical complexity of properties at the level of neurons and neural networks. As far as consciousness goes, (...) class='Hi'>neural network firing patterns triggered by axon-to-dendrite synaptic chemical transmissions are the fundamental correlates of consciousness. There is no need to look elsewhere. (shrink)

How do minds emerge from developing brains? According to the representational features of cortex are built from the dynamic interaction between neural growth mechanisms and environmentally derived neural activity. Contrary to popular selectionist models that emphasize regressive mechanisms, the neurobiological evidence suggests that this growth is a progressive increase in the representational properties of cortex. The interaction between the environment and neural growth results in a flexible type of learning: minimizes the need for prespecification in accordance with (...) recent neurobiological evidence that the developing cerebral cortex is largely free of domain-specific structure. Instead, the representational properties of cortex are built by the nature of the problem domain confronting it. This uniquely powerful and general learning strategy undermines the central assumption of classical learnability theory, that the learning properties of a system can be deduced from a fixed computational architecture. Neural constructivism suggests that the evolutionary emergence of neocortex in mammals is a progression toward more flexible representational structures, in contrast to the popular view of cortical evolution as an increase in innate, specialized circuits. Human cortical postnatal development is also more extensive and protracted than generally supposed, suggesting that cortex has evolved so as to maximize the capacity of environmental structure to shape its structure and function through constructive learning. (shrink)

We begin by distinguishing computationalism from a number of other theses that are sometimes conflated with it. We also distinguish between several important kinds of computation: computation in a generic sense, digital computation, and analog computation. Then, we defend a weak version of computationalism—neural processes are computations in the generic sense. After that, we reject on empirical grounds the common assimilation of neural computation to either analog or digital computation, concluding that neural computation is sui generis. Analog (...) computation requires continuous signals; digital computation requires strings of digits. But current neuroscientific evidence indicates that typical neural signals, such as spike trains, are graded like continuous signals but are constituted by discrete functional elements (spikes); thus, typical neural signals are neither continuous signals nor strings of digits. It follows that neural computation is sui generis. Finally, we highlight three important consequences of a proper understanding of neural computation for the theory of cognition. First, understanding neural computation requires a specially designed mathematical theory (or theories) rather than the mathematical theories of analog or digital computation. Second, several popular views about neural computation turn out to be incorrect. Third, computational theories of cognition that rely on non-neural notions of computation ought to be replaced or reinterpreted in terms of neural computation. (shrink)

This book brings together an international group of neuroscientists and philosophers who are investigating how the content of subjective experience is...