Molecular control of cell fate in the neural crest: the sympathoadrenal lineage.
Over the past five years, new insights have been gained into the biology of the SA lineage. These advances have been powered by the development of immunologic methods to isolate embryonic SA progenitors from fetal adrenal glands and sympathetic ganglia. Analysis of these embryonic progenitors has confirmed many of the ideas derived from earlier studies of postnatal cells, but has necessitated several revisions in our thinking, as well. First, embryonic SA progenitors appear to be distinct from mature SIF cells, a cell type initially postulated to be the central intermediate in the SA lineage. Second, FGF, not NGF, appears to be an important early influence on neuronal fate; NGF responsiveness appears relatively late in differentiation. Third, the development of both sympathetic neurons and adrenal chromaffin cells is not a one-step process, but rather involves a series of events, in which the cells change their responsiveness to growth factors and glucocorticoids. Fourth, emerging circumstantial evidence suggests that SA progenitors may have additional developmental potentials. Finally, new insights have been gained into the molecular mechanisms that underlie both the differentiation of SA progenitors and their determination from earlier multipotent neural crest cells. These advances have made the SA progenitor a well-defined system for studying the molecular control of cell fate in a vertebrate neurogenic precursor cell. The analysis of the SA lineage at the cell biological level has raised several interesting molecular questions for future investigation. In the neuronal branch of the SA lineage, how is the acquisition of NGF-responsiveness and NGF-dependence controlled, and what is the relationship of these events to the expression of p140trk and p75? In the chromaffin branch of the pathway, which molecules control the timing of PNMT expression? In the uncommitted SA progenitor, what is the molecular basis of the antagonism between the competing neuronal and chromaffin pathways of differentiation, and how does commitment to neuronal differentiation occur? Can SA progenitors differentiate to enteric neurons in vitro, and which differentiation and survival factors control this phenotype, as well as the other classical neurotransmitter and neuropeptide phenotypes expressed by SA derivatives? What are the roles of MASH1 and other regulatory genes in controlling early stages in neural crest cell determination, and how is the expression of these molecules in turn controlled? How much of the genetic regulatory network controlling neuronal differentiation in Drosophila has been conserved in vertebrates?(ABSTRACT TRUNCATED AT 400 WORDS)
Anderson
D J
DJ
Howard Hughes Medical Institute, Division of Biology, California Institute of Technology, Pasadena 91125.
D000313:Adrenal Medulla / Q000166:cytology / Q000196:embryology*; D000818:Animals; D002454:Cell Differentiation; D006133:Growth Substances / Q000502:physiology; D006801:Humans; D009432:Neural Crest / Q000166:cytology / Q000502:physiology*; D009474:Neurons / Q000166:cytology / Q000502:physiology*; D013234:Stem Cells / Q000166:cytology / Q000502:physiology; D013564:Sympathetic Nervous System / Q000166:cytology / Q000196:embryology*
D006133:Growth Substances