AP‐2 is a recent significant addition to the list of transcription factors that have been demonstrated by targeted gene disruption to be essential for normal development. Two recent reports of AP‐2 null mutant mice(1,2) indicate that AP‐2 holds a key position in the network of genes and proteins controlling developmental pattern and morphogenesis, and that it is particularly important for development of the cranial region and for midline fusions.

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)

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)

Stigma is a factor of diseases of craniofacial disfigurement, associated with negative health outcomes. Psychosocial interventions can improve the “illness” experience. The law can improve care by framing patients' rights, defining physicians' obligations to make psychological referrals, and fostering an activist orientation among patients.

The concept of craniofacial difference refers to a set of innate or acquired features causing facial abnormalities. While craniofacial difference is usually understood as an individual fact and is currently overlooked in the definitions of disability that govern disability policies, this study addresses it in its disregarded social dimensions, as shown in a case of the Supreme Court of Canada in 2021. The study then proposes a theological reflection on how the craniofacial anomaly destabilizes certain cultural patterns (...) that guide our visions of the world and how it invites us to engage in a different relationship to reality and meaning. (shrink)

The practice of modern craniomaxillofacial surgery has been defined by emergent technologies allowing for the acquisition, storage, utilization, and transfer of massive amounts of sensitive and identifiable patient data. This alone has thrust providers into an unlikely and unprecedented role as the stewards of vast databases of digital information. This data powers the potent surgical tool of virtual surgical planning, a method by which craniomaxillofacial surgeons plan and simulate procedural outcomes in a digital environment. Further complicating this new terrain is (...) the involvement of third‐party contractors—a necessary presence in bringing raw data to bear in the office, virtual space, and operating room. The individual privileges and responsibilities of patients, providers, and vendors towards data are situated within the most recent U.S. court rulings and regulations. This paper offers guidance for overseeing the safe and responsible transfer to third‐party contractors, and provides suggestions for negotiating the trinary relationship between physicians, their patients, and the vendors offering this transformative technology. (shrink)

Significant progress in the molecular investigation of endogenous bioelectric signals during pattern formation in growing tissues has been enabled by recently developed techniques. Ion flows and voltage gradients produced by ion channels and pumps are key regulators of cell proliferation, migration, and differentiation. Now, instructive roles for bioelectrical gradients in embryogenesis, regeneration, and neoplasm are being revealed through the use of fluorescent voltage reporters and functional experiments using well‐characterized channel mutants. Transmembrane voltage gradients (Vmem) determine anatomical polarity and function as (...) master regulators during appendage regeneration and embryonic left‐right patterning. A state‐of‐the‐art recent study reveals that they can also serve as prepatterns for gene expression domains during craniofacial patterning. Continued development of novel tools and better ways to think about physical controls of cell‐cell interactions will lead to mastery of the morphogenetic information stored in physiological networks. This will enable fundamental advances in basic understanding of growth and form, as well as transformative biomedical applications in regenerative medicine. (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)

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)

Central sensitization and related neurochemical mechanisms are also induced in V nociceptive pathways after craniofacial injury or inflammation. Their characteristics raise additional possibilities that may explain some of the phenomena outlined by coderre & katz, dickenson, and wiesenfeld-hallin et al. They also underscore the need for therapeutic approaches to reduce nociceptive inputs to the CNS or their neuroplastic effects which can potentially enhance post-traumatic pain.

The recent discovery of a phenomenon of craniofacial growth, called craniofacial contraction, throws a new light on the process of hominization. The main interest of this discovery lies in a growth principle combining the different craniofacial units, that is to say, the neurocranium, the chondrocranium and the splanchnocranium. Until recent years, these different parts were considered as neighbouring element without any morphogenic or morphodynamic connection. But now, we know that the morphogenesis of the base of the skull (...) governs that of the face. This basicranial morphogenesis is the occipital flexion. It generates morphogenic correlations with the face since embryogenesis. The ontogenic pathway of this phenomenon is the craniofacial contraction. It concerns embryonic dynamics connected with the spatial development of the embryonic neural system, the neural tube. These morphodynamics are common to each primate species, but they are differenciated by the amplitude of the embryonic contraction. We ask ourself the question: is hominization of the neurocephalic embryogenesis, that is the craniofacial contraction, plausible over a very long period, with gradual and chaotic evolutionary pathways, or, on the contrary, is the complexity of such an embryonic phenomenon, a limiting factor generating determined and predictible ontogenic thresholds? The study of extant and fossil primate skulls demonstrates that species are organized around 6 levels of embryonic contraction, which, starting from 60 millions years, evolve from the less to the most contracted skull. Among each ontogenic level, living and fossil species develop from the same embryonic system but between both levels, the embryos suddenly are reorganized. Therefore, I have defined an evolutive ontogenic unity, that is the fundamental ontogenesia. The cephalic pole has a fundamental ontogenesis, meaning that, beyond the diversities, we can see the same contraction in many living and extinct species. The ontogenic diversities are the result of the microevolution and are not predictible. In such a perspective, the ontogenic morphodynamics evolve with chaotic trajectories. But, between two embryonic levels, or two fundamental ontogeneses, evolutionary modalities are different. Eventually, from 60 millions years to XXth century, we observe the same phenomenon than during human ontogenesis; hominization of the cephalic pole is a craniofacial contraction. The evolutive pathway is stable, whatever the number of thresholds, the cranial shape changes but the ontogenic trajectory is preserved. This is a macroevolution because the embryonic system is reorganized. The logics of the phenomenon are an increasing dynamization, the human ontogenesis is the more unstable and the longer morphodynamics to stabilize the craniofacial contraction. To conclude, hominization is an iteration of an ontogenic process when embryos reach successive dynamic thresholds. The attractors are neither static, periodic, nor chaotic because the successive ontogenic trajectories are themselves in a stable evolutive trajectory, and the results with increasing contraction, complexified neocortical tissues and cephalocaudal reorganization are predictible. During hominization, irreversibility and innovations do not emerge with chaotic determinism, but with harmonic determinism in association with the correlations established between the embryonic tissues. When the system is destabilized, the embryonic systems do not forget the previous ontogenic pattern, on the contrary, they develop the pattern with new dynamical conditions. This sort of phenomenon is not described in the sciences of complexity. In the present case, we are in front of many millions years and the necessity to propose new concepts such as a new familly of attractors, namely the harmonic attractors. (shrink)

This book explores numerous ways in which vulgar language, grotesque appearances, and horrific experiences affect us in our relationships with others and with ourselves. Its compelling case studies and revealing interviews bring together ideas and issues that are a lingering, but unexplored, focus in psychotherapy literature. The grotesque and the vulgar are major inhabitants of the vast unconscious. Their variations and haunting presence are anticipated and reflected in the transactions of everyday life. So too do they manifest themselves in our (...) social institutions, maintaining their presence in the seven lively arts as much as in mental hospitals, rehabilitation facilities, and psychotherapy practices. Most of all, the grotesque and vulgar challenge the contemporary search for meaning and sanity. This book will help the psychotherapist better deal with the rich soil of grotesqueness and vulgarity in the interplay between the psychotherapy patient and the experiential world. Reading it will open new vistas of treatment possibilities. As each contributing author explores the potentialities and obstacles inherent in the competing and complementing forces of the grotesque and socially condoned sensibilities, you will learn about the value of the grotesque in the consultation room. You will further learn how the flaunted and unconscious vulgarities of everyday life enrich the creative vision inherent in therapeutic conversations. Most important, you will be challenged by what it means to abide with the sometimes pesky vulgar and grotesque guises in each of your client's lives. Here's a sample of what you'll find in Inhabitants of the Unconscious: The Grotesque and the Vulgar in Everyday Life: Louis Fierman's recollection of his treatment of a Nazi soldier, which offers fascinating therapeutic possibilities when issues of the grotesqueare at hand an extraordinary analysis of the role of the grotesque in artwork, with special attention paid to the work of Hieronymus Bosch a fascinating look at Sigmund Freud's perspective on the grotesque&#; and what it says about Freud himself the remarkable formative experiences of children with craniofacial difference &#;an exposition that will enrich your therapeutic interventions with children and adolescents who face atypical challenges extraordinary case studies&#;by Robert Marchesani about his therapeutic endeavors with a Vietnam veteran caught in the aftermath of his incestuous past and by E. Mark Stern about a dying woman who was unable to detach from, but ultimately vivified by an unyielding masochistic fixation. (shrink)

The mouthparts of anuran tadpoles are highly derived compared to those of caecilians or salamanders. The suprarostral cartilages support the tadpole's upper beak; the infrarostral cartilages support the lower beak. Both supra‐ and infrarostral cartilages are absent in other vertebrates. These differences reflect the evolutionary origin of a derived feeding mode in anuran tadpoles. We suggest that these unique cartilages stem from the evolution of new articulations within preexisting cartilages, rather than novel cartilage condensations. We propose testing this hypothesis through (...) a search for similarities in the development of the suprarostral and infrarostral cartilage articulations and of the primary jaw joint. In Xenopus, the gene zax is expressed in a region corresponding to the infrarostral cartilage. This gene is related to the bapx1‐gene, which regulates jaw joint development. Further investigation of these genes, as well as other genes with joint‐related functions, in anuran craniofacial development may provide a connection between the morphological diversity seen in the vertebrate head and the corresponding diversity in genetic regulatory processes. We believe that the evolution of larval jaws in anurans may shed light on the general evolutionary mechanisms of how new articulations, not only in the jaw region, could have arisen in the vertebrate skull. BioEssays 27: 526–532, 2005. © 2005 Wiley periodicals, Inc. (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)

The Salivaomics Knowledge Base (SKB) is designed to serve as a computational infrastructure that can permit global exploration and utilization of data and information relevant to salivaomics. SKB is created by aligning (1) the saliva biomarker discovery and validation resources at UCLA with (2) the ontology resources developed by the OBO (Open Biomedical Ontologies) Foundry, including a new Saliva Ontology (SALO). We define the Saliva Ontology (SALO; http://www.skb.ucla.edu/SALO/) as a consensus-based controlled vocabulary of terms and relations dedicated to the salivaomics (...) domain and to saliva-related diagnostics following the principles of the OBO (Open Biomedical Ontologies) Foundry. The Saliva Ontology is an ongoing exploratory initiative. The ontology will be used to facilitate salivaomics data retrieval and integration across multiple fields of research together with data analysis and data mining. The ontology will be tested through its ability to serve the annotation ('tagging') of a representative corpus of salivaomics research literature that is to be incorporated into the SKB. Background Saliva (oral fluid) is an emerging biofluid for non-invasive diagnostics used in the detection of human diseases. The need to advance saliva research is strongly emphasized by the National Institute of Dental and Craniofacial Research (NIDCR), and is included in the NIDCR's 2004- 2009 expert panel long-term research agenda [1]. The ability to monitor health status, disease onset, progression, recurrence and treatment outcome through noninvasive means is highly important to advancing health care management. Saliva is a perfect medium to be explored for personalized individual medicine including diagnostics, offering a non-invasive, easy to obtain means for detecting and monitoring diseases. Saliva testing potentially allows the patient to collect their own saliva samples at home, yielding convenience for the patient and savings in health costs, and facilitating multiple sampling. Specimen collection is less objectionable to patients and easier in children and elderly individuals. Due to these advantages. (shrink)

There is a need recognized by the National Institute of Dental & Craniofacial Research and the National Cancer Institute to advance basic, translational and clinical saliva research. The goal of the Salivaomics Knowledge Base (SKB) is to create a data management system and web resource constructed to support human salivaomics research. To maximize the utility of the SKB for retrieval, integration and analysis of data, we have developed the Saliva Ontology and SDxMart. This article reviews the informatics advances in (...) saliva diagnostics made possible by the Saliva Ontology and SDxMart. (shrink)

ObjectivePregnancy leads to long-lasting changes in brain structure for healthy women; however, little is known regarding alterations in the cortical features of pregnant women with malformed fetuses. Isolated clefts of the lip and/or palate (ICL/P) are the most common congenital anomaly in the craniofacial region, which is highly gene-associated. We speculated that pregnant women carrying fetuses with ICL/P may have associated risk genes and specific brain changes during pregnancy.MethodsIn this study, we investigated T1-weighted brain magnetic resonance imaging data from (...) 48 pregnant women: 24 women carrying fetuses with ICL/P (ICL/P group) and 24 women carrying normal fetuses (normal controls), then explored intergroup differences in gray matter volume (GMV), cortical thickness (CT) and cortical complexity (gyrification).ResultsCompared with controls, the ICL/P group had decreased total intracranial volume (TIV) than normal controls; besides, they exhibited increased GMV in the left cuneus, decreased GMV in the right superior temporal gyrus; increased CT in the left precuneus and left superior parietal gyrus, decreased CT involving parsopercularis, fusiform, middle temporal in the left hemisphere and supramarginal, precentral gyrus (PreCG) in the right hemisphere; increased gyrification in the left insula and PreCG, the left middle temporal, and the right supratemporal gyrus.ConclusionPregnant women with ICL/P fetuses had brain morphology changes involving language, auditory, vision, and sensory cortex, which may be their special brain changes compared to normal pregnant women. This study may provide clues for the early detection of fetuses with ICL/P, and be vital for preconception and prenatal counseling with non-invasive methods. (shrink)

Contemporary medicine views health as the individual’s physical, mental, and social well-being. Oral health plays a crucial role in one’s well-being, as the oral cavity and its surrounding regions execute essential functions in verbal and nonverbal communication, sensing, digestion, and significantly contribute to aesthetic appearance. The multifaceted nature of the notion of oral health, as well as the patient’s needs and autonomous will result in various treatment options for the same oral state, favouring often contrasting ethical values and different aspects (...) of oral health. The objective of this article is to suggest alternative treatment strategies in dentistry with respect to the following factors: extent of rehabilitation, preserving one’s anatomical structures, aesthetic outcome, number of sessions, patient autonomy. Additionally, this article describes the suggested treatment strategies in an ethical context and determines the conditions of their employment. The suggested treatment strategies are divided in two categories, extensive treatment strategies focusing on the patient’s entire craniofacial complex, while specific treatment strategies focus on specific paramount issues. (shrink)

Background: Facial proportionality and symmetry are positively associated with perceived levels of facial attractiveness. -/- Objective: The aims of this study were to confirm and extend the association of proportionality with perceived levels of attractiveness and character traits and determine differences in attractiveness and character ratings between "anomalous" and "typical" faces using a large dataset. -/- Methods: Ratings of 597 unique individuals from the Chicago Face Database were used. A formula was developed as a proxy of relative horizontal proportionality, where (...) a proportionality score of "0" indicated perfect proportionality and more negative scores indicated less proportionality. Faces were categorized as "anomalous" or "typical" by 2 independent reviewers based on physical features. -/- Results: Across the ratings for all faces, Spearman correlations revealed greater proportionality was associated with attractiveness ( ρ = 0.292, P < 0.001) and trustworthiness ( ρ = 0.193, P < 0.001), while lesser proportionality was associated with impressions of anger (ρ = 0.132, P = 0.001), dominance (ρ = 0.259, P < 0.001), and threateningness ( ρ = 0.234, P < 0.001). Mann-Whitney U tests revealed the typical cohort had significantly higher levels of proportionality (-13.98 versus -15.14, P = 0.030) and ratings of attractiveness (3.39 versus 2.99, P < 0.001) and trustworthiness (3.48 versus 3.35, P < 0.001). -/- Conclusions: This study demonstrated that facial proportionality is not only significantly associated with higher ratings of attractiveness, but also associated with judgements of trustworthiness. Proportionality plays a role in evoking negative attributions of personality characteristics to people with facial anomalies. (shrink)