The genetic and acquired developmental defects of the craniofacial region are among the most poignant and the least understood developmental defects. The long term objective of this project is to begin to understand at the molecular level the complex series of events involved in the formation of the craniofacial skeleton. Unlike trunk skeletal tissue, the skeletal tissue in the craniofacial region is formed mostly from a mesenchyme derived from the neural crest (NC). The first skeletal tissue to appear in the developing head is cartilage. The differentiation of these cells has been shown to be dependent in avian embryos upon prior interactions with the epithelia during or after migration. It has been reported recently that type II collagen is present transiently in the basement membrane associated with the early cranial ectoderm at the sites where these interactions take place. Meckel's cartilage, a structure in the mandibular arch, requires early inductive interactions between the cranial NC and the mandibular and cranial ectoderm for its formation. This structure serves as a template for the subsequent mandibular bone formation. An integrated approach combining tissue recombination techniques and recombinant DNA technology will be used to study and compare the relationships between the molecular events and the morphological events leading to the formation of the Meckel's cartilage of avian embryos. Regulation of various extracellular matrix proteins (including type I, type II, and IX collagens, and the core protein of the chondroitin sulfate proteoglycan) in the developing head will be studied using cytoplasmic dot hybridization and in situ hybridization techniques. Specific questions to be addressed include: 1) which cells synthesize the type II collagen present in the basement membrane associated with the early cranial ectoderm; 2) when and where do the precursor cells for Meckel's cartilage first accumulate type II collagen mRNA; 3) what is the spatial and temporal pattern of accumulation of the other mRNAs and how does this relate to the subsequent formation of the mandible. Tissue recombination experiments will be used to study whether or not the mesencephalic NC cells require postmigratory interactions with the mandibular epithelium, and to study the mechanisms involved in the spatial organization of the skeletal tissue in the mandible, specifically to determine whether inhibitory effects of the mandibular epithelium are involved.
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