The Society for Craniofacial Genetics and Developmental Biology 45th Annual Meeting

The Society for Craniofacial Genetics and Developmental Biology (SCGDB) held its 45th Annual Meeting at the Sanford Consortium for Regenerative Medicine at the University of California, San Diego on October 20th–21st, 2022. The meeting included presentation of the SCGDB Distinguished Scientists in Craniofacial Research Awards to Drs. Ralph Marcucio and Loydie Jerome-Majewska and four scientific sessions that highlighted new discoveries in signaling in craniofacial development, genomics of craniofacial development, human genetics of craniofacial development and translational and regenerative approaches in craniofacial biology. The meeting also included workshops on analysis of single cell RNA sequencing datasets and using human sequencing data from the Gabriella Miller Kids First Pediatric Research Program. There were 110 faculty and trainees in attendance that represent a diverse group of researchers from all career stages in the fields of developmental biology and genetics. The meeting, which also included outdoor poster presentations, provided opportunities for participant interactions and discussions, thus strengthening the SCGDB community.     

The Society for Craniofacial Genetics and Developmental Biology 41st Annual Meeting

The mission of the Society for Craniofacial Genetics and Developmental Biology (SCGDB) is to promote education, research, and communication about normal and abnormal development of the tissues and organs of the head. The SCGDB welcomes as members undergraduate students, graduate students, postdoctoral researchers, medical and dental practitioners, scientists, and academicians who possess an interest in craniofacial biology. Each year our members come together to share their novel findings, build upon, and challenge current knowledge of craniofacial biology.     

Gene discovery in craniofacial development and disease--cashing in your chips

An unbiased, polygenic approach is needed to unravel the complex molecular bases of craniofacial development and disease. DNA microarrays, the current paradigm of genome-wide analysis, permit the simultaneous study of many thousands of genes, the ready identification of candidate molecules and pathways, and the compilation of gene expression profiles for whole systems--pathologic and embryonic alike. We survey the existing literature applying microarrays to craniofacial biology and highlight the value of animal models, particularly mice and chickens, to understanding molecular regulation in the craniofacial complex. We also emphasize the importance of functional studies and high-throughput assays to extracting useful data from microarray output. It is our goal to help put researchers and clinicians on the same page as microarray technology moves into the forefront of craniofacial biology.     

Cranial neural crest cells on the move: their roles in craniofacial development

The craniofacial region is assembled through the active migration of cells and the rearrangement and sculpting of facial prominences and pharyngeal arches, which consequently make it particularly susceptible to a large number of birth defects. Genetic, molecular, and cellular processes must be temporally and spatially regulated to culminate in the three-dimension structures of the face. The starting constituent for the majority of skeletal and connective tissues in the face is a pluripotent population of cells, the cranial neural crest cells (NCCs). In this review we discuss the newest scientific findings in the development of the craniofacial complex as related to NCCs. Furthermore, we present recent findings on NCC diseases called neurocristopathies and, in doing so, provide clinicians with new tools for understanding a growing number of craniofacial genetic disorders.     

Molecular insights into the function, fate, and prospects of stem cells

This article forms a review and an appraisal of the third annual meeting of the International Society for Stem Cell Research (http://www.isscr.org), held in San Francisco on June 23-25, 2005. The focus of the meeting was recent advances in stem cell biology. More than 2,000 scientists from around the world met to discuss stem cell research, clinical applications, and the ethical hurdles facing the field. Major topics highlighted during the meeting included the self-renewal and differentiation of embryonic stem cells as well as adult stem cells. Presentations included diverse topics such as cancer stem cells, tissue-specific stem cells, technology development, and clinical aspects of stem cells. Given the excitement the field has generated, linking basic stem cell research and clinical applications was paramount for discussion at the meeting. With the current resources in molecular biology research, improvements in genetic engineering, postgenomic capabilities, and biotechnological advances, it appears timely that stem cell biology research is headed toward making a major therapeutic contribution to human health.     

The impact of Drew Noden's work on our understanding of craniofacial musculoskeletal integration

The classical anatomist Drew Noden spearheaded craniofacial research, laying the foundation for our modern molecular understanding of development, evolution, and disorders of the craniofacial skeleton. His work revealed the origin of cephalic musculature and the role of cranial neural crest (CNC) in early formation and patterning of the head musculoskeletal structures. Much of modern cranial tendon research advances a foundation of knowledge that Noden built using classical quail-chick transplantation experiments. This elegant avian chimeric system involves grafting of donor quail cells into host chick embryos to identify the cell types they can form and their interactions with the surrounding tissues. In this review, we will give a brief background of vertebrate head formation and the impact of CNC on the patterning, development, and evolution of the head musculoskeletal attachments. Using the zebrafish as a model system, we will discuss examples of modifications of craniofacial structures in evolution with a special focus on the role of tendon and ligaments. Lastly, we will discuss pathologies in craniofacial tendons and the importance of understanding the molecular and cellular dynamics during craniofacial tendon development in human disease.     

The present-day state of studies dedicated to the problem of hemoblastoses

The authors describe the main results of Hemablastoses project studies conducted within the framework of Federal target scientific and technical program in 2000-2004. They adduce research concept and the ways of solving the problem of hemoblastoses in the nearest years. Principally new approaches to the diagnostics and treatment of blood system diseases were developed; they were based on studies of cell and molecular mechanisms of their occurrence and development by methods of molecular biology and genetic engineering.     

Craniofacial ciliopathies: A new classification for craniofacial disorders

Craniofacial anomalies are some of the most variable and common defects affecting the population. Herein, we examine a group of craniofacial disorders that are the result of defects in primary cilia; ubiquitous, microtubule-based organelles that transduce molecular signals and facilitate the interactions between the cell and its environment. Based on the frequent appearance of craniofacial phenotypes in diseases born from defective primary cilia (ciliopathies) we propose a new class of craniofacial disorders referred to as craniofacial ciliopathies. We explore the most frequent phenotypes associated with ciliopathic conditions and the ciliary gene mutations responsible for craniofacial defects. Finally, we propose that some non-classified disorders may now be classified as craniofacial ciliopathies.     

What is anatomy? Implications for anatomy as a discipline and for Clinical Anatomy as a journal

Anatomy as a discipline is explored against a background of the growth of scientific knowledge and developments within modern universities. The structural overtones of anatomic approaches provide intellectual cohesion for the approaches of complementary disciplines. When anatomy departments function in a transdisciplinary manner, they encompass a range of areas from molecular biology to functional anatomy and biological anthropology. Suggestions are made for a journal, such as Clinical Anatomy, to provide stimulus for the further development of anatomy as a coherent discipline.     

Ion channels: their structure, function and control – an overview

In the past two decades, investigations on ion channels have made remarkable progress. Since the development of patch clamp recording techniques in 1980s, investigators have been able to detect the real-time behaviour of single channels on many kinds of cell membrane. Rapid advances in molecular biology techniques led to the cloning and identification of a variety of ion channel genes, many of which have been the targets of knock-outs or disruptions. Recent significant progress in structural biology has enabled us to grasp the molecular architecture of some ion channels, and their structure–function relationship. In this special issue, knowledge from these various approaches are summarized and presented by seven specialists in the respective fields. This discussion took place on 24 March, 2003, during the joint annual scientific sessions of the 80th Japanese Physiological and the 76th Pharmacological Society meetings in Fukuoka, Japan. The symposium was held just after the outbreak of hostilities in Iraq, and some of the speakers originally invited could not participate. Fortunately, two excellent substitute speakers took part (Drs Zamponi and Findlay on Ca²⁺ channels).     

Kazrin, and its binding partners ARVCF- and delta-catenin, are required for Xenopus laevis craniofacial development

The novel adaptor protein Kazrin associates with multifunctional entities including p120-subfamily members (ARVCF-, delta-, and p0071-catenin). Critical contributions of Kazrin to development or homeostasis are indicated with respect to ectoderm formation, integrity and keratinocyte differentiation, whereas its presence in varied tissues suggests broader roles. We find that Kazrin is maternally loaded, is expressed across development and becomes enriched in the forming head. Kazrin's potential contributions to craniofacial development were probed by means of knockdown in the prospective anterior neural region. Cartilaginous head structures as well as eyes on injected sides were reduced in size, with molecular markers suggesting an impact upon neural crest cell establishment and migration. Similar effects followed the depletion of ARVCF (or delta-catenin), with Kazrin:ARVCF functional interplay supported upon ARVCF partial rescue of Kazrin knockdown phenotypes. Thus, Kazrin and its associating ARVCF- and delta-catenins, are required to form craniofacial tissues originating from cranial neural crest and precordal plate.     

T cell receptor specificity and mimotopes.

Degeneracy rather than unique ligand specificity seems to guide T cell functions. This view has evolved from analyses of T cell development and responses in vivo, as well as studies with synthetic molecular libraries in vitro, and has opened new prospects both for understanding T cell biology and for applied immunology.     

Ypel1: a novel nuclear protein that induces an epithelial-like morphology in fibroblasts

BACKGROUND: Embryonic development depends on the regulation of cell morphology and behaviour to carry out morphogenesis. One example of this is the development of the face, which is constructed from independent blocks of tissue that must grow in a coordinated way and then fuse to form a continuous tissue. RESULTS: We have isolated a novel gene of unknown function from mouse and quail embryos in a search for genes involved in craniofacial development. Sequence analysis of this gene, known as Ypel1, demonstrates a striking level of amino acid conservation between vertebrates and invertebrates but no significant homology with any other characterized genes. Ypel1 is expressed in the ventral half of early embryos including the branchial arches from which the face derives. Ypel1 localizes to the nucleus, and transfection into fibroblasts induces an epithelial-like transition, which is accompanied by alterations to the cytoskeleton and cell adhesion machinery. In addition, human YPEL1 localizes to chromosome 22q11.2, a region associated with a number of syndromes involving malformation of the craniofacial complex. CONCLUSION: These data suggest a role in regulation of cellular morphology and behaviour that is important for development of the craniofacial complex.     

Postnatal Msx1 expression pattern in craniofacial, axial, and appendicular skeleton of transgenic mice from the first week until the second year.

Phenotypes associated with Msx1 mutations have established the prominent role of this divergent homeogene in skeletal patterning. Previous studies have been achieved during antenatal development in relation with the early death of null mutant mice. Therefore, the present study is devoted to Msx1 homeogene in the postnatal craniofacial, axial, and appendicular skeleton. A knock-in transgenic mouse line was studied from the first postnatal week until 15 months. Whole-mount beta-galactosidase enzymology identified Msx1 protein expression pattern. Maintained expression of Msx1 was observed in growing and adult mice, specifically in the sites where Msx1 plays an early morphogenetic role during initial skeletal patterning. These included the craniofacial sutures, autopodium, mandible, and alveolar bone. Furthermore, active membranous and endochondral bone formation involved Msx1 in the entire skeleton. Histologic sections showed that progenitor as well as differentiating and differentiated cells of all the bone cell lineages could express the Msx1 protein (chondrocytes, osteoblasts, tartrate-resistant acid phosphatase positive osteoclasts and chondroclasts). Recent developments in the genetic and developmental biology of skeletal morphogenesis demonstrate that genes critical for development are jointly expressed in discrete embryonic signalling and growth centers, the enamel knot in teeth, the cranial suture in skull morphogenesis, and the progress zone in the limb buds. The present study suggests that these signalling pathways are jointly important throughout the entire lifetime with an exquisite site-specificity spatially related to early patterning.     

Cellular and molecular mechanisms in the development of a cleft lip and/or cleft palate; insights from zebrafish (Danio rerio)

Human cleft lip and/or palate (CLP) are immediately recognizable congenital abnormalities of the face. Lip and palate develop from facial primordia through the coordinated activities of ectodermal epithelium and neural crest cells (NCCs) derived from ectomesenchyme tissue. Subtle changes in the regulatory mechanisms of NCC or ectodermal epithelial cells can result in CLP. Genetic and environmental contributions or a combination of both play a significant role in the progression of CLP. Model organisms provide us with a wealth of information in understanding the pathophysiology and genetic etiology of this complex disease. Small teleost, zebrafish (Danio rerio) is one of the popular model in craniofacial developmental biology. The short generation time and large number of optically transparent, easily manipulated embryos increase the value of zebrafish to identify novel candidate genes and gene regulatory networks underlying craniofacial development. In addition, it is widely used to identify the mechanisms of environmental teratogens and in therapeutic drug screening. Here, we discuss the value of zebrafish as a model to understand epithelial and NCC induced ectomesenchymal cell activities during early palate morphogenesis and robustness of the zebrafish in modern research on identifying the genetic and environmental etiological factors of CLP.     

活细胞内单分子视踪检测研究进展

对细胞生物学与分子生物学中有关分子事件和相互作用的认识,大部分都是在非活体条件下、忽略分子事件全过程所得到的研究结果,并且这些研究结果是基于被研究的所有单分子在相同的环境以相同的方式运动这个不真实的假设.随着量子点(QDs)等新的荧光物质和抗体模拟物等小分子抗体连接后制备成的新型探针的出现,以及转导外源性荧光探针进入活细胞内的各种方法的发展,再加上优良的荧光成像系统和快速灵敏的荧光采集系统在生命科学中的应用,使得视踪活细胞单个生物分子的轨迹、运动及多种单分子的相互作用成为现实.单分子水平的视踪研究为细胞生物学和分子生物学的研究打开了新的篇章.概述了目前活细胞内单分子视踪技术的研究进展并评价了其发展前景.     

Recent advances in craniofacial morphogenesis.

Craniofacial malformations are involved in three fourths of all congenital birth defects in humans, affecting the development of head, face, or neck. Tremendous progress in the study of craniofacial development has been made that places this field at the forefront of biomedical research. A concerted effort among evolutionary and developmental biologists, human geneticists, and tissue engineers has revealed important information on the molecular mechanisms that are crucial for the patterning and formation of craniofacial structures. Here, we highlight recent advances in our understanding of evo-devo as it relates to craniofacial morphogenesis, fate determination of cranial neural crest cells, and specific signaling pathways in regulating tissue-tissue interactions during patterning of craniofacial apparatus and the morphogenesis of tooth, mandible, and palate. Together, these findings will be beneficial for the understanding, treatment, and prevention of human congenital malformations and establish the foundation for craniofacial tissue regeneration.     

Getting to the (c)ore of knowledge: mining biomedical literature

Literature mining is the process of extracting and combining facts from scientific publications. In recent years, many computer programs have been designed to extract various molecular biology findings from Medline abstracts or full-text articles. The present article describes the range of text mining techniques that have been applied to scientific documents. It divides 'automated reading' into four general subtasks: text categorization, named entity tagging, fact extraction, and collection-wide analysis. Literature mining offers powerful methods to support knowledge discovery and the construction of topic maps and ontologies. An overview is given of recent developments in medical language processing. Special attention is given to the domain particularities of molecular biology, and the emerging synergy between literature mining and molecular databases accessible through Internet.     

Increased levels of apoptosis in the prefusion neural folds underlie the craniofacial disorder, Treacher Collins syndrome

Treacher Collins syndrome (TCS) is an autosomal dominant disorder of human craniofacial development that results from loss-of-function mutations in the gene TCOF1. Although this gene has been demonstrated to encode the nucleolar phosphoprotein treacle, the developmental mechanism underlying TCS remains elusive, particularly as expression studies have shown that the murine orthologue, Tcof1, is widely expressed. To investigate the molecular pathogenesis of TCS, we replaced exon 1 of Tcof1 with a neomycin-resistance cassette via homologous recombination in embryonic stem cells. Tcof1 heterozygous mice die perinatally as a result of severe craniofacial anomalies that include agenesis of the nasal passages, abnormal development of the maxilla, exencephaly and anophthalmia. These defects arise due to a massive increase in the levels of apoptosis in the prefusion neural folds, which are the site of the highest levels of Tcof1 expression. Our results demonstrate that TCS arises from haploinsufficiency of a protein that plays a crucial role in craniofacial development and indicate that correct dosage of treacle is essential for survival of cephalic neural crest cells.     

Development of the upper lip: morphogenetic and molecular mechanisms.

The vertebrate upper lip forms from initially freely projecting maxillary, medial nasal, and lateral nasal prominences at the rostral and lateral boundaries of the primitive oral cavity. These facial prominences arise during early embryogenesis from ventrally migrating neural crest cells in combination with the head ectoderm and mesoderm and undergo directed growth and expansion around the nasal pits to actively fuse with each other. Initial fusion is between lateral and medial nasal processes and is followed by fusion between maxillary and medial nasal processes. Fusion between these prominences involves active epithelial filopodial and adhering interactions as well as programmed cell death. Slight defects in growth and patterning of the facial mesenchyme or epithelial fusion result in cleft lip with or without cleft palate, the most common and disfiguring craniofacial birth defect. Recent studies of craniofacial development in animal models have identified components of several major signaling pathways, including Bmp, Fgf, Shh, and Wnt signaling, that are critical for proper midfacial morphogenesis and/or lip fusion. There is also accumulating evidence that these signaling pathways cross-regulate genetically as well as crosstalk intracellularly to control cell proliferation and tissue patterning. This review will summarize the current understanding of the basic morphogenetic processes and molecular mechanisms underlying upper lip development and discuss the complex interactions of the various signaling pathways and challenges for understanding cleft lip pathogenesis.