title: Distinct subpopulations of enteric neuronal progenitors defined by time of development, sympathoadrenal lineage markers and Mash-1-dependence.
abstract: Enteric and sympathetic neurons have previously been proposed to be lineally related. We present independent lines of evidence that suggest that enteric neurons arise from at least two lineages, only one of which expresses markers in common with sympathoadrenal cells. In the rat, sympathoadrenal markers are expressed, in the same order as in sympathetic neurons, by a subset of enteric neuronal precursors, which also transiently express tyrosine hydroxylase. If this precursor pool is eliminated in vitro by complement-mediated lysis, enteric neurons continue to develop; however, none of these are serotonergic. In the mouse, the Mash-1-/- mutation, which eliminates sympathetic neurons, also prevents the development of enteric serotonergic neurons. Other enteric neuronal populations, however, including those that contain calcitonin gene related peptide are present. Enteric tyrosine hydroxylase-containing cells co-express Mash-1 and are eliminated by the Mash-1-/- mutation, consistent with the idea that in the mouse, as in the rat, these precursors generate serotonergic neurons. Serotonergic neurons are generated early in development, while calcitonin gene related peptide-containing enteric neurons are generated much later. These data suggest that enteric neurons are derived from at least two progenitor lineages. One transiently expresses sympathoadrenal markers, is Mash-1-dependent, and generates early-born enteric neurons, some of which are serotonergic. The other is Mash-1-independent, does not express sympathoadrenal markers, and generates late-born enteric neurons, some of which contain calcitonin gene related peptide.
authors.affiliation: Department of Anatomy and Cell Biology, Columbia University College of Physicians and Surgeons, New York, NY 10032, USA.
authors.forename: E
authors.initials: E
authors.lastname: Blaugrund
authors.forename: T D
authors.initials: TD
authors.lastname: Pham
authors.forename: V M
authors.initials: VM
authors.lastname: Tennyson
authors.forename: L
authors.initials: L
authors.lastname: Lo
authors.forename: L
authors.initials: L
authors.lastname: Sommer
authors.forename: D J
authors.initials: DJ
authors.lastname: Anderson
authors.forename: M D
authors.initials: MD
authors.lastname: Gershon
mesh_terms: D000818:Animals; D000943:Antigens, Differentiation / Q000378:metabolism; D001483:Base Sequence; D051792:Basic Helix-Loop-Helix Proteins; D017931:DNA Primers / Q000235:genetics; D004268:DNA-Binding Proteins / Q000235:genetics*; D017615:Enteric Nervous System / Q000166:cytology* / Q000196:embryology* / Q000378:metabolism*; D005260:Female; D018507:Gene Expression Regulation, Developmental; D007150:Immunohistochemistry; D066298:In Vitro Techniques; D051379:Mice; D008810:Mice, Inbred C57BL; D008817:Mice, Mutant Strains; D008969:Molecular Sequence Data; D009154:Mutation; D009474:Neurons / Q000145:classification / Q000166:cytology* / Q000378:metabolism; D011247:Pregnancy; D051381:Rats; D017207:Rats, Sprague-Dawley; D013234:Stem Cells / Q000145:classification / Q000166:cytology* / Q000378:metabolism; D013564:Sympathetic Nervous System / Q000166:cytology / Q000196:embryology / Q000378:metabolism; D013997:Time Factors; D014157:Transcription Factors / Q000235:genetics*
chemical_list: D000943:Antigens, Differentiation; D051792:Basic Helix-Loop-Helix Proteins; D017931:DNA Primers; D004268:DNA-Binding Proteins; D014157:Transcription Factors; C499317:Ascl1 protein, mouse; C499318:Ascl1 protein, rat