TGF-β superfamily and mouse craniofacial development:: Interplay of morphogenetic proteins and receptor signaling controls normal formation of the face

The combination of brain, sensory organs, craniofacial skeleton, and cephalic musculature within the head makes it a uniquely complex structure. The sensory organs of the head are far more intricate than in the rest of the body, and originate from neurogenic placodes, structures found only in the embryonic head region. The head muscles, with the exception of the tongue musculature, are formed from unsegmented paraxial and prechordal mesoderm, in striking contrast to somatic muscles, which are derived from epithelial somites of a segmental nature. Interspecies comparisons show that facial bones are the most variable parts of the skeleton, contributing to formation of such a complex phenotypic feature as facial expression, one of the strongest visual stimuli used for the recognition of individuals, especially among primates (Kendrick et al., 2001). Skeletal components such as teeth, membrane bone, and secondary cartilage are tissue types located exclusively in the head (clavicles being the only exception). One of the greatest discoveries in developmental biology was the finding that the craniofacial skeleton is intimately connected with neural tissue-the vast majority of craniofacial bones and cartilages are, in fact, derivatives of neural crest cells (Northcutt and Gans, 1983). Why ectodermal cells that usually give rise to peripheral nervous system, neural ganglia, neuroendocrine cells, and melanocytes can also form structures that are derived strictly from the mesoderm elsewhere in the body skeleton is a challenging developmental and evolutionary question. The fact that the craniofacial skeleton is a mixture of bones and cartilage originating from the cranial neural crest and those originating from the mesoderm brings new insights to craniofacial development, since it is now clear that molecular processes involved in chondrogenesis, osteogenesis, and fracture healing are remarkably different between these two groups of skeletal compounds (Helms and Schneider, 2003). Furthermore, birth defects with a craniofacial component belong to the most frequent malformations in humans, thus representing a considerable health, psychological, and economic burden to affected families, as well as to society. The treatment of these disorders is often impossible, or represents a painful, stressful, and lengthy multistep procedure. Thus, an understanding of the biological processes underlying craniofacial development and physiology can bring a substantial contribution to current medical knowledge. Recent advances in genetics and molecular biology (e.g., vertebrate genome projects, new bioinformatic tools, microarray assays, gene knockout technology, tissue-specific gene targeting, in vivo imaging and microimaging) have produced an exponential growth of knowledge of embryonic development, and a substantial amount of data on head morphogenesis has accumulated over the past decade. Unlike ever before, the nature of these new techniques has opened windows into cellular and molecular mechanisms underlying the body plan creation, resulting in frequent redefinitions and updates in embryology, as well as in classification of developmental diseases. Inherently, this information boom results in increased branching and complexity in the scientific literature, raising the need to consolidate new data into logical and vital blocks of knowledge. Bone morphogenetic proteins and related peptides from the transforming growth factor beta (TGF-β) superfamily represent a distinct group of growth factors involved in head embryogenesis. They play roles in processes essential for craniofacial development: neural crest formation and migration, and cartilage and bone physiology. Their involvement in embryonic angiogenesis further underlines their importance in normal morphogenesis and related developmental diseases. This chapter is a compilation of the current knowledge of the role of members of the TGF-β superfamily and their signaling pathways in facial development. © 2005 Elsevier Inc. All rights reserved.