Craniofacial Biology Research Articles

Book review

Understanding Craniofacial Anomalies: The Etiopathogenesis of Craniosynostosis and Facial Clefting. Edited by Mark P. Mooney and Michael I. Siegel. (583 pp.; ISBN: 047138724X, hardback) May 2002: Wiley. ‘Your face is a book, where men may read strange matters.’ Macbeth For all those involved in the care of children with craniofacial deformities, perhaps the most difficult question we are faced with daily is ‘why?’ Parents, caretakers and other healthcare providers turn to us for all the answers to all their questions regarding what went wrong in the developmental process of a newborn's gestation. Most clinicians, be they paediatricians, geneticists or surgeons, have a reasonable answer that is used again and again to provide an explanation for why a given anomaly has occurred. Of course, although there are those in the disciplines above who have true expertise in the field of craniofacial biology, most of us know just enough developmental biology to comfortably recite a bit of embryology combined with a bit of molecular biology to provide a well-described, yet highly generalized answer. Although of course I cannot speak for all, I know that each time I gave such an answer, I feel a longing to gain a better understanding of the aetiopathology of the condition, to gain more insight into the genetic background and to better understand the normal stages of embryogenesis of that particular component of the face. Thanks to this superb book, all of the above is now possible. Edited by two renowned scientists in the field of craniofacial biology, Drs Mark Mooney and Michael Siegel, this text is an outstanding compilation of chapters on the aetiology of craniofacial disorders, particularly craniosynostosis and facial clefting. The book, described as a tour-de-force by Professor Michael Cohen, is well organized into seven sections to cover efficiently the concepts of classification and terminology, embryogenesis, facial, calvarial and skull base growth, and dysmorphology, animal models and molecular biology. The editors of this book should be praised for two achievements, both of which provide the foundation for the book's excellence. First, the authors chosen to write the individual chapters are all themselves experts in the field. When experienced people such as Geoffrey Sperber, Ethylin Wang Jabs, Joan Richtsmeier and Harold Slavkin, among others, come together to produce such a work, the information contained is sure to be of great interest to the reader. Second, the editors have ensured that the tone and context of each chapter was written in a language with enough scientific detail to be of use to those involved in laboratory research, but simultaneously written in a way to be understandable and readily comprehended by clinicians as well. In summary, this book is a ‘must-read’ for all those who strive to understand craniofacial deformities. I am certain that it will provide a wonderful clinical context for those involved in basic science, and equally a wonderful scientific context for those involved in clinical work. This book has enhanced my knowledge on several levels, and I extend my thanks to all those who made it possible.

Assessment of mandibular growth and response to orthopedic treatment with 3-dimensional magnetic resonance images

Three-dimensional (3D) craniofacial images are commonly used in clinical studies in orthodontics to study developmental and morphologic relationships. We used 3D magnetic resonance imaging to study relationships among craniofacial components during the pubertal growth spurt and in response to Fränkel appliance therapy. The sample for this prospective study was 156 high-resolution magnetic resonance images with 1 mm isotropic voxel resolution of 78 subjects taken initially (T1) and 18 +/- 1 months (T2) after treatment or an observation period. The subjects were Brazilian children; 28 were treated and 25 were untreated for Class II malocclusion, and 25 were untreated with normal occlusions. A Procrustes geometric transformation of 3D skeletal landmarks was used to assess growth or treatment alterations from T1 to T2. The landmarks were located on the mandibular rami and the other craniofacial parts specifically related to the mandibular growth (the middle cranial fossae and the posterior part of the bilateral nasomaxilla). This allowed visualization of the entire volumetric dataset with an interactive 3D display. Statistically significant differences were found in the relative 3D skeletal growth directions from T1 to T2 for treated vs untreated Class II children (Bonferroni-adjusted P < .001) and for treated Class II vs normal-occlusion subjects ( P < .001). The major differences in the treated group were increased mandibular rami vertical dimensions and more forward rami relative to the posterior nasomaxilla and the middle cranial fossae. Principal component analysis made it possible to show individual variability and group differences in the principal dimensions of skeletal change. These methods are generalizable to other imaging techniques and 3D samples, and significantly enhance the potential of systematically controlled data collection and analysis of bony structures in 3 dimensions for quantitative assessment of patient parameters in craniofacial biology.

Interaction between Smad 3 and Dishevelled in murine embryonic craniofacial mesenchymal cells

To determine the in vivo interaction between Smad 3 and Dishevelled-1. Cell culture transfection followed by immunoprecipitation with specific antibodies. The Department of Molecular, Cellular, and Craniofacial Biology, Birth Defects Center, University of Louisville. Overexpression of myc-Smad 3. Western blotting of anti-Dishevelled immunoprecipitates for Smad 3. Smad 3 and Dishevelled isoforms-1, -2, and -3 all bind Smad 3 in glutathione-S-transferase (GST) pull-down assays and Smad 3 binds to Dishevelled-1 in vivo. Stimulation of the transforming growth factor beta (TGFbeta) pathway leads to increased binding of Smad 3 and Dishevelled-1 in vivo. Smad 3 binds all three known isoforms of Dishevelled and binds Dishevelled 1 in vivo. TGFbeta signaling modulates the interaction between Smad 3 and Dishevelled-1.

Study on tooth development, past, present, and future.

For decades, the understanding of craniofacial development has been a central issue in odontology and developmental biology. As a consequence, a significant number of deformities are being studied for their variety of genotype and phenotype. Although there is little doubt about the essential roles of homeobox genes, transcription factors, and growth factors, we now know at least the fundamental strategy of craniofacial biology. The tooth as an organ performs a whole range of functions, each of which is truly indispensable for the maintenance of life. The possession of teeth is, therefore, obviously coupled with the complication of the natural structure of an individual organism. In the following, we shall focus on a brief history of tooth studies and some suggestions for obtaining a full understanding of teeth in the future.

Book reviews: 1

Book reviews: 1

Editorial Consultants

Clinical Orthodontics and Research–Genes, Growth and Development owes its success in publishing the highest quality reports in orthodontics and craniofacial biology to the authors who submit their best work, the editorial board, but specifically, to the Editorial Consultants who referee a large number of manuscripts. These leaders of the specialty and distinguished experts in their field have been most generous with their time for the articles that appeared in Volume 5.

Gene expression profiling by DNA microarray technology.

Methods in molecular and genetic biology have provided important clues to elucidate the complex mechanisms of oral and craniofacial development and pathogenesis of diseases. It has become increasingly clear that a biological phenotype is a result of multiple factors involving a large number of regulatory genes, while a single nucleotide mutation can cause various degrees of oral and craniofacial abnormalities. These oral and craniofacial problems often present a challenge to the molecular screening process. Recent advances in microarray-based technologies allow for large-scale gene expression analysis in a single experiment, which have been applied to genome-wide assays, mutational analysis, drug discovery, developmental biology, and molecular analysis of various diseases. This review introduces the basic principle and some modifications of techniques and materials used in microarray technology, as well as currently available microarray data analysis strategies. Microarray technology can be applied to the soon-to-be-available human genome database and will be a powerful research tool for those inquiring into specific problems associated with oral and craniofacial biology.

New developments in craniofacial surgery research.

The recent explosion in our understanding of developmental biology and genetics has enhanced our understanding of craniofacial biology. While it is not possible to summarize all new developments in craniofacial research, this article will review three areas: fetal models and surgery for craniofacial disorders, the biology of distraction osteogenesis, and the molecular mechanisms of cranial suture fusion. Numerous models of craniofacial disorders have been described, including small, short gestation and large, long gestation. The benefits and shortcomings of each are discussed. In addition, we discuss recent studies investigating the molecular mechanisms of mandibular distraction osteogenesis. Finally, we present a review of recent advances in the understanding of mechanisms of craniosynostosis, with particular emphasis on the biology of programmed cranial suture fusion in rodents.

Molecular biology experimental strategies for craniofacial-oral-dental dysmorphology.

This paper is a minireview of molecular biology experimental strategies for problems within craniofacial-oral-dental biology. Many of these strategies have already made remarkable contributions towards understanding the complex developmental processes associated with craniofacial biology. For example, the utilization of these strategies has resulted in the successful mapping of approximately 70 genes related to craniofacial anomalies (e.g., Pax, retinoic acid receptors, cadhedrins, aggrecan, cell adhesion molecules, substrate adhesion molecules, etc.), 30 genes related to dental tissue disorders (e.g., BMPs, bone morphogenetic proteins; dentin phosphoproteins, dentin sialoglycoproteins, enamelins, amelogenins), 20 genes related to facial clefting defects (e.g., Hox genes, transforming growth factor alpha), and 3 genes related to craniosynostosis (e.g., Msx-2). This minireview highlights selected examples of scientific progress derived from the following experimental strategies: (i) molecular approaches to the organization of the mouse and human chromosomes, with the mapping of specific gene sequences linked to human diseases (e.g., amelogenesis imperfecta, Boston type craniosynostosis, Rieger's syndrome, Treacher Collins syndrome); (ii) reverse genetic approaches for studies of gene function; (iii) homologous recombinations and the advances from "knock-out" transgenic mouse models for human craniofacial-oral-dental diseases; (iv) mutational analyses of congenital craniofacial-oral-dental dysmorphogenesis; (v) structural biology studies using computer-assisted molecular modeling for protein-protein, protein-nucleic acid and protein-inorganic interactions; (vi) computer modeling of genetic paradigms; and (vii) a cluster of newer methodologies including computer-assisted morphometry, new microinjection techniques, new cell membrane and intracellular dyes, and a number of new RNA and DNA viral constructs for the delivery of genes to enhance the resolution of cell fate maps, cell lineage studies and gene therapy approaches to human diseases.

Complex Craniofacial Problems—A Guide to Analysis and Treatment

Part 1 The human evolution and definition of growth, development and anomalies: history of craniofacial surgery evolutionary biology and the study of craniofacial growth, development and dysmorphology recent evolution of craniofacial structure classification of craniofacial anomalies. Part 2 Initial analysis and concerns: radiological analysis and visualization of craniofacial anomalies genetics and craniofacial syndromes patient-parent-surgeon issues concerning craniofacial surgery a philiosophical approach to craniofacial surgery. Part 3 Procedures and management: anaesthetic management in craniofacial surgery surgical techniques for the correction of craniosynostosis and neurocranial asymmetry reconstructive problems in cleft lip and palate and craniofacial malformations hypertelorism correction oculoplastic surgery in craniofacial surgery analysis and principles of surgery for Treacher Collins syndrome analysis and reconstruction of hemifacial microsomia orthognathic considerations of maxillary and mandibular surgery vascular malformations of the head and neck craniofacial trauma and its management management of craniofacial and cranial base tumors microvascular surgical applications to the craniofacial area applications of craniofacial techniques to aesthetic surgery post-operative management following major craniofacial surgery management of complications of craniofacial surgery. Part 4 New techniques and procedures: applications of autogeneous bone grafting for craniofacial problems the use of alloplastic materials for craniofacial anomalies the use of tissue expansion in craniofacial surgery unusual problems and situations new horizons in craniofacial surgery.

Finite element-based cephalometric analysis.

The finite element method has proven to be a useful tool for morphometric analysis in craniofacial biology. However, few attempts have been made to adapt this method for routine use by clinicians. The CEFEA program incorporates the advanced features of the finite element method but bypasses the detailed understanding of the engineering and mathematics previously required to interpret results. The program uses the color graphics display of common personal computers to show size change, shape change, and angle of maximum change. These are pictured as colored triangles of clinically relevant regions between pre- and mid- or posttreatment lateral headfilms. The program is designed to have features of interest in both clinical practice and research.

Internal organization in the human jaw muscles.

The human jaw muscles are essential to mastication and play an important part in craniofacial growth. They contribute to dental and articular forces, deform the mandible, and, like other tissues, are subject to disorders, often manifested as pain. The literature describes how their contraction is controlled by the nervous system, and how their general structure and function contribute to craniofacial biology, but there has been little appraisal of their internal organization. Most of these muscles are not simple; they are multipennate, complexly layered, and divided by aponeuroses. This arrangement provides substantial means for differential contraction. In many ways, jaw muscle fibers are intrinsically dissimilar from those found in other skeletal muscles, because they are arranged in homogeneous clusters and generally reveal type I or type II histochemical profiles. Most are type I and are distributed preferentially in the anterior and deeper parts of the jaw closers. Additionally, most motor unit (MU) territories are smaller than those in the limbs. There is circumstantial evidence for intramuscular partitioning based in part on innervation by primary muscle nerve branches. During normal function. MU recruitment and the rate coding of MU firing in human jaw muscles follow the general principles established for the limbs, but even here they differ in important respects. Jaw muscle MUs do not have stable force recruitment thresholds and seem to rely more on rate coding than on sequential unit recruitment to grade the amplitude of muscle contraction. Unlike those in the limbs, their twitch tensions correlate weakly with MU fatiguability and contraction speed, probably because there are so few slow, fatigue-resistant MUs in the jaw muscles. Moreover, the type I fibers that are present in such large numbers do not contract as slowly as normally expected. To complicate matters, estimation of jaw MU twitch tensions is extremely difficult, because it is affected by the location used to measure the twitch, the background firing rate, muscle coactivation, and regional, intramuscular mechanics. Finally, there have been very few systematic studies of jaw MU reflex behavior. The most recent have concentrated on exteroceptive suppression and suggest that MU inhibition following intra- and perioral stimulation depends on the location of the MU, its background firing rate, the timing of the stimulus, and the task used to drive the unit. Task dependency is a common feature of human jaw MU behavior, reflecting interaction between peripheral sensory information from orofacial and muscle afferents and corticobulbar drive.(ABSTRACT TRUNCATED AT 400 WORDS)

The mechanism of parenchymal cell proliferation in adult male mouse submandibular gland (SMG): Yang Chai. Los Angeles: Graduate Program in Craniofacial Biology, School of Dentistry University of Southern California, 1991

The mechanism of parenchymal cell proliferation in adult male mouse submandibular gland (SMG): Yang Chai. Los Angeles: Graduate Program in Craniofacial Biology, School of Dentistry University of Southern California, 1991

Data Analysis in Craniofacial Biology with Special Emphasis on Longitudinal Studies

Recommendations are made for strengthening data description and analysis in craniofacial biology. Special emphasis is placed on longitudinal data, and PC programs for accomplishing appropriate analyses in this context are described and made available to interested readers. Some more general recommendations are treated in less detail. These include the effective description of data using stem-and-leaf displays and/or boxplots, the use of decision-analytic methods in the management of patients with dentofacial deformities, and the valid application of certain statistical methods in single-subject studies. Finally, it is conjectured that computer-intensive methods such as randomization tests and jackknifing will play an increasingly prominent role in craniofacial research.

Data Analysis in Craniofacial Biology with Special Emphasis on Longitudinal Studies

Recommendations are made for strengthening data description and analysis in craniofacial biology. Special emphasis is placed on longitudinal data, and PC programs for accomplishing appropriate analyses in this context are described and made available to interested readers. Some more general recommendations are treated in less detail. These include the effective description of data using stem-and-leaf displays and/or boxplots, the use of decision-analytic methods in the management of patients with dentofacial deformities, and the valid application of certain statistical methods in single-subject studies. Finally, it is conjectured that computer-intensive methods such as randomization tests and jackknifing will play an increasingly prominent role in craniofacial research.

Evolutionary Issues in Craniofacial Biology

Evolutionary Issues in Craniofacial Biology

Evolutionary Issues in Craniofacial Biology

This overview discusses evolution in the context of craniofacial development and developmental processes. It begins with a discussion of the origins of the craniofacial tissues in the dentine and bone of the dermal denticles of the Ordovician jawless vertebrates, followed by a brief discussion of the mechanisms responsible for the evolution of the jaws and the origin of vertebrate dentition. Then the unique neural crest cell origin of the craniofacial skeletogenic and odontogenic tissues is discussed with emphasis on the constancy of rostrocaudal polarization of the skeletogenic cranial neural crest. Given this constancy, the variation in the craniofacial region that occurs across the vertebrates must arise because of epigenetic interactions that evoke the differentiation of craniofacial tissues. These are discussed in the context of epigenetic cascades of epithelial-mesenchymal interactions and how such epigenetic control has itself evolved. Although several mechanisms are considered, emphasis is placed on variation of the timing of development processes (heterochrony).

Appropriate Animal Models for Craniofacial Biology

The use of animal models in craniofacial biology has helped make significant contributions toward the clinical and surgical management of patients with craniofacial disorders. The present paper discusses some problems associated with choosing appropriate animal models for research in human craniofacial morphology and offers suggestions for determining the most appropriate model. Three levels of appropriate animal model choices are suggested: (1) the "generic mammalian" animal model, useful for investigating the problems of bone biology and generalized mammalian craniofacial growth mechanisms; (2) the "phylogenetically closer" animal model, useful for investigating the influence of experimental manipulations on the general primate craniofacial growth pattern; and (3) "fitting" the appropriate animal model to specific regional craniofacial growth patterns or anatomic conditions of interest. The continued, intelligent use of animal models in craniofacial investigations depends heavily on understanding and appreciating the information that can be derived from the "appropriate" animal model.

Craniofacial development: a summing up.

ABSTRACT It is convenient to distinguish between three related problems in development: cell differentiation; pattern formation, which is about spatial organization; and morphogenesis in the strict sense, which is about change in form, particularly of cell sheets, but includes cell migration (Wolpert, 1981; Wolpert &amp; Stein, 1984). All these need to be linked to gene action. If one looks forward over the next five to ten years then the future of craniofacial biology lies in molecular cell biology. This is not to say that all the problems at the tissue level have been solved, quite the contrary, but rather that the emphasis must now be at the cell and molecular level.

Research on craniofacial genetics and developmental biology: implications for the future of academic dentistry

The literature of biology abounds in awe-inspiring acts of iridescent genius. Although a law of nature is phrased in abstract language and is itself devoid of passion and sensibility, the history of its discovery may be an epic worthy of Homer, every page of which bears the stamp of the personality of people. Clearly, scientific truth can be defended by dispassionate logic, but its discovery cannot be promoted this way. The human factor in the creative equation is an important aspect. The discovery of the principles that now form the foundation of developmental craniofacial biology is a story of irony and paradox. Although much progress has been made in many scientific endeavors, many questions regarding craniofacial growth and development remain unanswered. One of the main problems encountered in studies of mammalian growth and development, specifically those dealing with developmental craniofacial biology, has been the apparent lack of application of advances in parallel fields of scientific endeavor. The time seems appropriate for commingling clinical problems with the recently acquired principles of cellular, molecular, and developmental biology.