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The UCSF Program
in Craniofacial and Mesenchymal Biology
FACULTY
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Morphogenesis
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Morphogenesis is a dynamic developmental process through which cells and tissues differentiate and grow into the complex anatomical structures that form an organism. In order for individual neural, skeletal, muscular, and vascular components to achieve their proper size, shape, orientation, and functional integration, embryonic progenitor populations require appropriate spatial and temporal signals. Our research focuses on the extent to which the neural crest, which is a mesenchymal stem cell population, serves as a source of spatiotemporal patterning information during craniofacial morphogenesis. The special patterning abilities of the cranial neural crest have been recognized for more than fifty years but precise molecular mechanisms through which they exert their effects remain obscure. Cranial neural crest cells originate along the dorsal margins of the developing neural tube, and they migrate extensively throughout the head. Their derivatives include cartilage, bone, dentine, sensory ganglia, glia, melanocytes, meninges, and a variety of connective tissues. Transplant experiments in diverse vertebrate taxa have offered persuasive evidence that cranial neural crest cells possess inherent programmatic information governing the anatomy of their own derivatives, especially cartilages and bones of the face and jaws.
In my lab, we have been developing an experimental chimeric system using two distinct avian species, quail and duck. This approach exploits the fact that as embryos, quail and duck are morphologically distinct and have considerably different rates of maturation, which provides a novel method for manipulating signals being conveyed between skeletal precursor cells and adjacent tissues such as muscles, nerves, and epidermis. In particular, exchanging premigratory cranial neural crest cells between quail and duck embryos permits progressively asynchronous donor mesenchyme and host tissues to interact with one another continuously from the moment they first meet. Consequent neural crest-mediated changes to molecular and histogenic programs of craniofacial development can then be observed. We are finding that within resultant chimeras, donor neural crest mesenchyme executes autonomous molecular programs and regulates gene expression in adjacent host tissues. This in turn, establishes when derivatives of the donor and those of the host undergo differentiation, and determines the size, shape, and location of anatomical structures from both the donor and the host. Thus, neural crest mesenchyme functions as a primary source of spatiotemporal patterning information during craniofacial development, and in this capacity has likely played an essential role in facilitating morphological change during the course of evolution. Identifying precise signaling mechanisms through which these mesenchymal stem cells exert their affects will be critical for devising molecular-based therapies that can induce repair and regeneration of anatomical complexes affected by congenital defects, disease, and trauma.
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Selected Publications
Smith, K. K. and R. A. Schneider. (1998) Have Gene Knockouts Caused Evolutionary Reversals in the Mammalian First Arch? BioEssays, 20(3):245-255.
Schneider, R. A. and J. A. Helms. 2003. The cellular and molecular origins of beak morphology. Science, 299:565-568.
Schneider, R. A. (in press). Developmental mechanisms facilitating the evolution of bills and quills. Journal of Anatomy.
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Osteoblast depositing
bone matrix |
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