Cell morphogenesis encompasses all processes required to establish a three-dimensional cell shape. Cells acquire the architecture specific to their developmental context by using the spatial information provided by internal or external cues. As a response to these signals, cells become reorganized and establish functionally distinct subcellular domains that ultimately lead to morphological changes. In its simplest form, cell morphogenesis results in the establishment of asymmetry along one axis, a cell polarity. Although cell polarity has been studied intensively in (...) budding yeast and epithelial cells, little is known about more complex modes of cell morphogenesis involving multiple axes. In this review we compare the regulation of cell morphogenesis of different genetically well-characterized cell types in Arabidopsis thaliana. BioEssays 20:20–29, 1998. © 1998 John Wiley & Sons, Inc. (shrink)

Cell morphogenesis encompasses all processes required to establish a three-dimensional cell shape. Cells acquire the architecture specific to their developmental context by using the spatial information provided by internal or external cues. As a response to these signals, cells become reorganized and establish functionally distinct subcellular domains that ultimately lead to morphological changes. In its simplest form, cell morphogenesis results in the establishment of asymmetry along one axis, a cell polarity. Although cell polarity has been studied intensively in (...) budding yeast and epithelial cells, little is known about more complex modes of cell morphogenesis involving multiple axes. In this review we compare the regulation of cell morphogenesis of different genetically well-characterized cell types in Arabidopsis thaliana. BioEssays 20:20–29, 1998. © 1998 John Wiley & Sons, Inc. (shrink)

Problems and Paradigms is a feature series devoted to discussions of major problems in biology. Past contributions have dealt with the selector gene hypothesis, problems of pattern formation, the phenomenon of paramutation, theories of aging, and the origins of life. In this article, Brian C. Goodwin discusses the problem of morphogenesis, in terms of the idea of the genetic program and in the light of recent findings.

The life cycle of Dictyostelium discoideum offers a unique opportunity to study signal transduction in eukaryotic cells at both the unicellular and multicellular levels of organization. Adding to the already extensive knowledge of the unicellular stages, classical and molecular genetics have begun to unravel transduction of signals controlling morphogenesis and behaviour (phototaxis and thermotaxis) in the multicellular ‘slug’ stage of the life cycle. Distributed over all seven genetic linkage groups are probably about 20, but possibly as many as 55, (...) genes of importance for slug behaviour. The encoded proteins appear from pharmacological studies and mutant phenotypes to govern transduction pathways involving the intracellular second messengers cyclic AMP, cyclic GMP, IP3 and Ca2+. Pathways from the photo‐ and thermoreceptors converge first with each other and thence, at the level of the second messengers, with those from extracellular tip activation (cyclic AMP) and inhibition (Slug Turning Factor and/or ammonia and/or adenosine) signals that control slug movement and morphogenesis. (shrink)

Epithelial development dictates the shape of an organism. The metamorphic development of a Drosophila leg precursor into an adult leg is a well‐defined example of epithelial morphogenesis that can be analyzed from the perspectives of genetics and molecular and cell biology. The steroid hormone 20‐hydroxyecdysone induces and regulates the entire process. Mutants affecting Drosophila leg morphogenesis characteristically have short thick legs (the malformed phenotype) resulting from a failure to execute normal cell shape changes at a specific stage of (...) development. Mutations that cause the malformed phenotype have already led to the identification and cloning of genes encoding transcription factors, a transmembrane serine protease presumably required for modification of the apical extracellular matrix, and components of the contractile cytoskeleton and adherens junctions. All of these products are required for the execution of normal changes in leg cell shape. (shrink)

The Drosophila salivary gland has emerged as an outstanding model system for the process of organ formation. Many of the component steps, from initial regional specification through cell specialization and morphogenesis, are known and many of the genes required for these different processes have been identified. The salivary gland is a relatively simple organ; the entire gland comprises of only two major cell types, which derive from a single contiguous primordium. Salivary cells cease dividing once they are specified, and (...) organ growth is achieved simply by an increase in size of individual cells, thus eliminating concerns about the potential unequal distribution of determinants during mitosis. Drosophila salivary glands form by the same cellular mechanisms as organs in higher organisms, including regulated cell shape changes, cell intercalation and directed cell migration. Thus, learning how these events are coordinated for tissue morphogenesis in an organism for which the genetic and molecular tools are unsurpassed should provide excellent paradigms for dissecting related processes in the more intricate organs of more complicated species. BioEssays 23:901–911, 2001. © 2001 John Wiley & Sons, 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)

The C. elegans male tail is being studied as a model to understand how genes specify the form of multicellular animals. Morphogenesis of the specialized male copulatory organ takes place in the last larval stages during male development. Genetic analysis is facilitated because the structure is not necessary for male viability or for strain propagation. Analysis of developmental mutants, isolated in several functional and morphological screens, has begun to reveal how fates of cells are determined in the cell lineages, (...) and how the specification of cell fates affects the morphology of the structure. Cytological studies in wild type and in mutants have been used to study the mechanism of pattern formation in the tail peripheral nervous system. The ultimate goal is to define the entire pathway leading to the male copulatory organ. (shrink)

The role of fixed charges present at the surface of biological membranes is usually described by the Gouy-Chapman-Grahame theory of the electric double-layer where the Grahame equation is applied independently on each side of the membrane and where the capacitive charges are disregarded. In this article, we generalize the Gouy-Chapman-Grahame theory by taking into account both intrinsic charges and capacitive charges, in the density value of the membrane surface charges. In the first part, we show that capacitive charges couple electrostatic (...) potentials present on both sides of the membrane. The intensity of this coupling depends both on the value of the membrane specific capacitance and the transmembrane electric potential difference. In the second part, we suggest some physiological implications of membrane electric double-layers. (shrink)

The Epic of Evolution is a course taught at Northern Arizona University. It engages the task of formulating a new epic myth that is based on the physical, natural, social, and cultural sciences. It aims to serve the need of providing meaning for human living in the vast and complex universe that the sciences now depict for us. It is an interdisciplinary effort in an academic setting that is often divided by specializations; it focuses on values in a climate of (...) relativism; and it concentrates on an enterprise for which there are few textbooks at hand. The course is presented in three segments: the cosmos before humans appeared, the human phenomenon, and scenarios for the future of evolution. (shrink)

The rapidly changing field of genetics affects society through advances in health-care and through implications of genetic research. This study addresses the impacts of new genetic discoveries and technologies on different segments of today's society. The book begins with a chapter on genetic complexity, and subsequent chapters discuss moral and ethical questions arising from today's genetics from the perspectives of health care professionals, the media, the general public, special interest groups and commercial interests.

Building on the emerging literature on the ethics of social enterprises (SEs), this paper advances the underexplored role of frontline workers (FLWs) as embedded agents at the interface between communities and SEs. Specifically, we uncover the subjectivity of FLWs as they navigate moral ambiguities while performing their professional roles, dealing with rules and regulations within the organizational hierarchy and living as members of local communities. Based on an inductive case study of a microfinance organization in Cameroon, we find that FLWs (...) engage in three rationalization strategies: cautious disengaging, safeguarding self-interest, and justifying relevance. Our findings offer a better understanding of the ethics of SEs by unpacking the subjectivity of FLWs. We highlight a bottom-up account of caring SEs, identify a boundary condition to subjectivity, and present a nuanced view of FLWs in embedded organizations. We also discuss the practical implications for SEs to improve their compassion and cater for the mental wellbeing of FLWs. (shrink)

By exploring whether nanotechnologies have the potential to generate green innovations, we consider the paradox between the negative and positive side-effects that could come with the development of nanotechnologies. Starting from the conceptual framework of green product innovation, the potential green innovation activity of more than 14,000 firms of the nanotech sector is investigated. Using a query-search method, their patenting activity is explored. Results first show that there is an increasing trend toward the creation of fundamental green knowledge by firms (...) involved in nanotechnologies; second, they demonstrate that energy efficiency is the main driver of green knowledge creation in the sector and third they reveal the main characteristics of nanotech firms creating green knowledge. Beyond their contribution to the debate between positive and negative outcomes of nanotechnology developments, these results also enrich the conceptual framework of green product innovation—a key route to achieving sustainability at the same time as growth. (shrink)

Society has historically not taken a benign view of genetic disease. The laws permitting sterilization of the mentally re tarded~ and those proscribing consanguineous marriages are but two examples. Indeed as far back as the 5th-10th centuries, B.C.E., consanguineous unions were outlawed (Leviticus XVIII, 6). Case law has traditionally tended toward the conservative. It is reactive rather than directive, exerting its influence only after an individual or group has sustained injury and brought suit. In contrast, state legislatures have not been (...) inhibited in enacting statutes. Many of their products can be characterized as hasty, unnecessary, ill-conceived, and based on the heart rather than the head. Moreover the lack of expert consultation sought has also been remarkable. One state legislature, for example, has advocated immunization for sickle cell anemia! Many others have enacted laws for the screening of inborn errors of metabolism, e.g., phenylketon uria, but have poorly defined the lines of responsibility to secure compliance. A spate of specific disease-related bills has emerged in the u.S. Congress, each seeking recognition and appropriations. Sickle cell anemia, hemophilia, Cooley's anemia and Tay-Sachs disease have been among the front-runners for support. Finally, in 1975, Congress has begun to examine an omnibus bill concerning all forms of genetic disease. The bill, termed the National Genetic Diseases Act is, however, still far from being enacted. (shrink)

Progressive supranuclear palsy is a movement disorder with prominent tau neuropathology. Brain diseases with abnormal tau deposits are called tauopathies, the most common of which is Alzheimer's disease. Environmental causes of tauopathies include repetitive head trauma associated with some sports. To identify common genetic variation contributing to risk for tauopathies, we carried out a genome-wide association study of 1,114 individuals with PSP and 3,247 controls followed by a second stage in which we genotyped 1,051 cases and 3,560 controls for the (...) stage 1 SNPs that yielded P ≤ 10-3. We found significant previously unidentified signals associated with PSP risk at STX6, EIF2AK3 and MOBP. We confirmed two independent variants in MAPT affecting risk for PSP, one of which influences MAPT brain expression. The genes implicated encode proteins for vesicle-membrane fusion at the Golgi-endosomal interface, for the endoplasmic reticulum unfolded protein response and for a myelin structural component. © 2011 Nature America, Inc. All rights reserved. (shrink)

BackgroundClinical ethical practice (CEP) is required for healthcare workers (HCWs) to improve health-care delivery. However, there are gaps between accepted ethical standards and CEP in Ethiopia. There have been limited studies conducted on CEP in the country. Therefore, this study aimed to determine the magnitude and associated factors of CEP among healthcare workers in healthcare facilities in Ethiopia.MethodFrom February to April 2021, a mixed-method study was conducted in 24 health facilities, combining quantitative and qualitative methods. Quantitative (survey questionnaire) and qualitative (...) (semi-structured interviews) data were collected. For quantitative and qualitative data analysis, Stata version 14 and Atlas.ti version 7 were utilized. Multiple logistic regression and thematic analysis for quantative and qualitative respectively used.ResultsFrom a total of 432 study participants, 407 HCWs were involved in the quantitative analysis, 36 participants were involved in five focus group discussions (FGDs), and eleven key informant interviews (KIIs) were involved in the qualitative analysis. The score of good CEP was 32.68%. Similarly, the scores of good knowledge and attitude were 33.50% and 25.31%, respectively. In the multiple logistic regression models, satisfaction with the current profession, availability of functional CECs, compassionate leaders, previously thought clinical ethics in pre-service education and good attitude were significant factors associated with CEP. Among these significant factors, knowledge, compassionate leaders, poor infrastructure, a conducive environment and positive attitudes were also determinants of CEP according to qualitative findings.ConclusionsThe CEP in health care services in Ethiopia is low. Satisfaction with the current profession, functional CECs, positive attitude, compassionate leaders and previously thought clinical ethics were significant factors associated with CEP. The Ministry of Health (MoH) should integrate interventions by considering CECs, compassionate leadership, and positive attitudes and enhance the knowledge of health professionals. Additionally, digitalization, intersectoral collaboration and institutionalization are important for promoting CEP. (shrink)

Actomyosin (actin‐myosin II complex)‐mediated contractile forces are central to the generation of multifaceted uni‐ and multi‐cellular material properties and dynamics such as cell division, migration, and tissue morphogenesis. In the present article, we summarize our recent researches addressing molecular mechanisms that ensure actomyosin‐mediated directional cell–cell junction remodeling, either shortening or extension, driving cell rearrangement for epithelial morphogenesis. Genetic perturbation clarified two points concerning cell–cell junction remodeling: an inhibitory mechanism against negative feedback in which actomyosin contractile forces, which are (...) well known to induce cell–cell junction shortening, can concomitantly alter actin dynamics, oppositely leading to perturbation of the shortening; and tricellular junctions as a point that organizes extension of new cell–cell junctions after shortening. These findings highlight the notion that cells develop underpinning mechanisms to transform the multi‐tasking property of actomyosin contractile forces into specific and proper cellular dynamics in space and time. (shrink)

Self-organization -- Organisms, finalisms, programs, machines -- Spinoza -- Judaism, determinism, and rationalities -- Fabricating the living -- Ethics.

This paper focuses on the inheritance of human handedness and cerebral lateralization within the more general context of structural biological asymmetries. The morphogenesis of asymmetrical structures, such as the heart in vertebrates, depends upon a complex interaction between information coded in the cytoplasm and in the genes, but the polarity of asymmetry seems to depend on the cytoplasmic rather than the genetic code. Indeed it is extremely difficult to find clear-cut examples in which thedirectionof an asymmetry is under genetic (...) control. As one possible case, there is some evidence that the direction, clockwise or counterclockwise, of rotation of the abdomen in certain mutant strains ofDrosophilais controlled by a particular gene locus, although there appears to be some degree of confusion on this point. By contrast, it is much easier to find examples in which thedegreebut not the direction of asymmetry is under genetic control. For instance, there is a mutant strain of mice in which half of the animals displaysitus inversusof the viscera. The proportion has remained at one half despite many years of inbreeding, suggesting that the mutant allele effectively cancels the normalsitusand allows the asymmetry to be specified in random fashion.Although this account does not deny that the right hemisphere of humans may be the more specialized for certain functions, it does attribute a leading or dominant role to the left hemisphere (at least in most individuals). We suggest that so-called “right-hemisphere” functions are essentially acquired by default, due to the left hemisphere's prior involvement with speech and skilled motor acts; we note, for instance, that these right-hemisphere functions include rather elementary perceptual processes. But perhaps the more critical prediction from our account is that the phenomenon of equipotentiality should be unidirectional: the right (lagging) hemisphere should be more disposed to take over left-hemisphere functions following early lesions than is the left (leading) hemisphere to take over right-hemisphere functions. We note preliminary evidence that this may be so. (shrink)

The theoretical biology movement originating in Britain in the early 1930’s and the biosemiotics movement which took off in Europe in the 1980’s have much in common. They are both committed to replacing the neo-Darwinian synthesis, and they have both invoked theories of signs to this end. Yet, while there has been some mutual appreciation and influence, particularly in the cases of Howard Pattee, René Thom, Kalevi Kull, Anton Markoš and Stuart Kauffman, for the most part, these movements have developed (...) independently of each other. Focussing on morphogenesis understood as vegetative semiosis, in this paper I will argue that the ideas of these movements are commensurate. Furthermore, synthesising them would enable us to see life processes as proto-narratives. Doing so will involve synthesising biohermeneutics, Peircian biosemiotics with Waddington’s theoretical biology and Piagetian genetic structuralism, and this, I claim, would strengthen the challenge of these traditions to mainstream biology. At the same time, this should contribute to overcoming the opposition between the sciences and the humanities, developing a broader tradition of Schellingian thought which involves developing the humanities and then demanding of the physical and biological sciences that they are consistent with and can make intelligible the emergence of humans as conceived by the humanities. (shrink)

We argue that the physics of complex materials and self-organizing processes should be made central to the biology of form. Rather than being encoded in genes, form emerges when cells and certain of their molecules mobilize physical forces, effects, and processes in a multicellular context. What is inherited from one generation to the next are not genetic programs for constructing organisms, but generative mechanisms of morphogenesis and pattern formation and the initial and boundary conditions for reproducing the specific traits (...) of a taxon. There is no inherent antagonism between this “physicalist” perspective and genetics, since physics acts on matter, and gene products are essential material components of living systems whose variability affects the systems’ parameters. We make this notion concrete by summarizing the concept of “dynamical patterning modules” (DPMs; Newman and Bhat, Phys Biol 5:1–14, 2008; Int J Dev Biol 53:693–705, 2009), an explicit physico-genetic framework for the origin and evolution of multicellular form in animals, as well as (when differences in interaction toolkit genes and applicable physical processes are taken into account) in multicellular plants (Hernández-Hernández et al., Int J Dev Biol 56:661–674, 2012). DPMs provide the missing link between development and evolution by revealing how genes acting in concert with physics can generate and transform morphology in a heritable fashion. (shrink)

Large‐scale patterns of correlated growth in development are partially driven by competition for metabolic and informational resources. It is argued that competition between organs for limited resources is an important mesoscale morphogenetic mechanism that produces fitness‐enhancing correlated growth. At the genetic level, the growth of individual characters appears independent, or “modular,” because patterns of expression and transcription are often highly localized, mutations have trait‐specific effects, and gene complexes can be co‐opted as a unit to produce novel traits. However, body parts (...) are known to interact over the course of ontogeny, and these reciprocal exchanges can be an important determinant of developmental outcomes. Genetic mechanisms underlie cell and tissue behaviors that allow organs to communicate with one another, but they also create evolutionarily adaptive competitive dynamics that are driven by physiological and biophysical processes. Advances in the understanding of competitive and closely related coordinative interactions across scales will complement existing research programs that emphasize the role of cellular mechanisms in morphogenesis. Study of the large‐scale order produced by competitive dynamics promises to facilitate advances in basic evolutionary and developmental biology, as well as applied research in fields such as bioengineering and regenerative medicine that aim to regulate patterning outcomes. (shrink)

Branching morphogenesis of epithelia is an important mechanism in mammalian development. The last decade has seen the identification of many signalling pathways and intracellular mechanisms that control epithelial branching. Tissue‐level mechanisms that space new branches out have, however, remained an unsolved problem. A recent publication by Nelson et al.1 suggests—if extrapolation from their novel and abstract culture system is valid—that branches may be spaced out by a system of mutual inhibition based on diffusion of TGFβ. Such a system would (...) allow a developing tree to arrange itself, without detailed genetic specification, by adaptive self‐organization. BioEssays 29: 205–207, 2007. © 2007 Wiley Periodicals, Inc. (shrink)

I attempt to characterize the relationship of classical experimental embryology (CEE) and molecular developmental biology and compare it to the much-discussed case of classical genetics. These sciences are treated here as discovery practices rather than as definitive forms of knowledge. I first show that CEE had some causal knowledge and hence was able to answer specific why?-questions. A paradigm was provided by the case of eye induction, perhaps CEE’s greatest success. The case of the famous Spemann-Mangold organizer is more difficult. (...) I argue that before the advent of molecular biology, knowledge of its causal role in development was very limited. As a result, there was no functional definition of the concept of organizer. I argue that, like the classical gene concept, it is best viewed as an operational concept. This means that an account of reduction such as Kim’s functional reduction, which is still a mainstay in scientific metaphysics, cannot work in these cases. Nonetheless, again like in the classical gene case, the operational concepts of CEE played an important heuristic role in the discovery of molecules involved in morphogenesis and cell differentiation. This was made possible by what I call inter-level investigative practices. These are practices that combine experimental manipulations targeting two (or more) different levels. I conclude that the two sciences are more closely related via their experimental practices than by any inter-level explanatory relations. (shrink)

Theories of the genetics underlying punctuated equilibrium (PE) have been vague to date. Here the developmental gene hypothesis is proposed, which states that: 1) developmental regulatory (DevReg) genes are responsible for the orchestration of metazoan morphogenesis and their extreme conservation and mutation intolerance generates the equilibrium or stasis present throughout much of the fossil record and 2) the accumulation of regulatory elements and recombination within these same genes—often derived from transposable elements—drives punctuated bursts of morphological divergence and speciation across (...) metazoa. This two‐part hypothesis helps to explain the features that characterize PE, providing a theoretical genetic basis for the once‐controversial theory. Also see the video abstract here https://youtu.be/C-fu-ks5yDs. (shrink)

The concept of plasticity has always been present in the history of developmental biology, both within the theory of epigenesis and within morphogenesis studies. However this tradition relies also upon a genetic conception of plasticity. Founded upon the concepts of ‘‘phenotypic plasticity’’ and ‘‘reaction norm,’’ this genetic conception focuses on the array of possible phenotypic change in relation to diversified environments. Another concept of plasticity can be found in recent publications by some developmental biologists (Gilbert, West-Eberhard). I argue that (...) these authors adopt a ‘‘broad conception of plasticity’’ that is closely related to a notion of development as something that is ongoing throughout an organism’s lifecycle, and has no clear-cut boundaries. However, I suggest that given a narrow conception of plasticity, one can define temporal boundaries for development that are linked to specific features of the morphological process, which are different from behavioral and physiological processes. (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)

Within the field of systems theory, the term robustness has typically been applied to different contexts such as automatic control, genetic networks, metabolic pathways, morphogenesis, and ecosystems. All these systems involve either man-made machines, or living organisms. In this chapter, we will consider music as a peculiar complex system, involving both the realm of machines and the realm of biology. We will discuss some of the properties of music experience in terms of different attributes of robustness, focusing in particular (...) on stability, the property enabling a complex system to maintain its function against a wide range of external and internal changes. We will provide examples of the human ability of isolating and maintaining stable information within the perceptual flow and despite changes in the external world that reach our perceptions, leading towards a characterization of robustness in music perception as referred both to the search for regularities and to the range of tolerance that perception admits to regularities. Finally, we will list four multiple interaction cycles that typically characterize music experience and that involve both internal properties of the organism and the environment. (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)

Significant progress has been made over the last decade in elucidating the mechanisms employed by receptor protein tyrosine kinases (RTKs) in transducing extracellular signals critical for the regulation of diverse cellular activities. Nevertheless, revealing the biological significance of a subset of the RTKs that contain catalytically inactive protein tyrosine kinase domains has proven more elusive. ErbB3 has served as the prototype for models of catalytically inactive RTK function, performing the role of signal diversification in heterodimeric receptor complexes with other ErbB (...) subfamily members. The receptor related to tyrosine kinases (RYK) is unique amongst the catalytically inactive RTKs. Based on structural or functional properties of the extracellular domain, RYK cannot be classified into an existing RTK subfamily. Recent genetic analyses of mouse Ryk and its Drosophila orthologue derailed have defined a role for this novel subfamily of receptors in the control of craniofacial development and neuronal pathway selection, respectively. Recent biochemical data lead us to propose a model that involves RYK in signal crosstalk and scaffold assembly with Eph receptors. This model is consistent with the established roles of Eph receptors and ephrins in craniofacial and nervous system morphogenesis. BioEssays 23:34–45, 2001. © 2001 John Wiley & Sons, Inc. (shrink)

The imaginal discs of Drosophila melanogaster, which form the adult epidermal structures, are a good experimental model for studying morphogenesis. The genital disc forms the terminalia, which are the most sexually dimorphic structures of the fly. Both sexes of Drosophila have a single genital disc formed by three primordia. The female genital primordium is derived from 8th abdominal segment and is located anteriorly, the anal primordium (10 and 11th abdominal segments) is located posteriorly, and the male genital primordium from (...) the 9th abdominal segment lies between them. In both sexes, only two of these three primordia develop to form the adult terminalia. The anal primordium develops in both sexes but, depending on the genetic sex, will form either male or female analia. However, only one of the genital primordia develops in each sex, forming either the male or the female genitalia. This depends on the genetic sex of the fly. Therefore, the genital disc is a very good experimental model of how the sex‐determination and homeotic genes — which determine cell identity — interact to direct the development of a population of cells into male or female terminalia. It has been proposed that the sexually dimorphic development of the genital disc is the result of an integrated genetic input, made up by the sex‐determination gene doublesex and the homeotic gene Abdominal‐B. This input acts by modulating the response to Hedgehog, Wingless, and Decapentaplegic morphogenetic signals. BioEssays 23:698–707, 2001. © 2001 John Wiley & Sons, Inc. (shrink)

Efforts from diverse disciplines, including evolutionary studies and biomechanical experiments, have yielded new insights into the genetic, signaling, and mechanical control of tooth formation and functions. Evidence from fossils and non‐model organisms has revealed that a common set of genes underlie tooth‐forming potential of epithelia, and changes in signaling environments subsequently result in specialized dentitions, maintenance of dental stem cells, and other phenotypic adaptations. In addition to chemical signaling, tissue forces generated through epithelial contraction, differential growth, and skeletal constraints act (...) in parallel to shape the tooth throughout development. Here recent advances in understanding dental development from these studies are reviewed and important gaps that can be filled through continued application of evolutionary and biomechanical approaches are discussed. (shrink)