Neural crest cells disperse during early vertebrate embryogenesis, localize precisely in various embryonic regions, and produce a variety of derivatives, including melanocytes, neurons and glia of the sensory, autonomic, and enteric nervous systems, neurosecretory cells, dental papillae, and other skeletal and connective tissues of the head and face. Genetic or developmental defects affecting crest cell behavior result in a variety of congenital malformations and diseases, such as craniofacial dysplasia, spina bifida, and phakomatoses. We wish to understand how localized environmental cues, encountered in interstitial spaces by dispersing crest cells, affect their developmental behavior. To this end, we propose to analyze the development of mouse embryos, homozygous for mutations (e.g. Patch, and piebald-lethal or lethal-spotting,) that adversely affect neural crest derivatives. Specifically, we will combine histochemical procedures and microscope-photometric measurements to compare the kinds, amounts and precise local distribution of extracellular matrix macromolecules in mutant mouse embryos and their normal littermates, at times and locations at which important crest cell morphogenetic events occur. By such comparisons, we hope to identify morphogenetically significant components of the interstitial matrix. To test the mode of action of identified matrix macromolecules, we will (i) isolate crest cell subpopulations with known developmental potentialities, using monoclonal antibodies against cell type-specific surface determinants, (ii) culture these cells on substrata containing matrix macromolecules with putative developmental signficance, and (iii) characterize the differentiative behavior of the cultured crest cells in response to the environmental cues that they encounter.
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