DISTINCT SUBPOPULATIONS OF ENTERIC NEURONAL PROGENITORS DEFINED BY TIME OF DEVELOPMENT, SYMPATHOADRENAL LINEAGE MARKERS AND MASH-1-DEPENDENCE

Enteric and sympathetic neurons have previously been proposed to be li neally related, We present independent lines of evidence that suggest that enteric neurons arise from at least two lineages, only one of whi ch expresses markers in common with sympathoadrenal cells, In the rat, sympathoadrenal markers are expressed, in the same order as in sympat hetic neurons, by a subset of enteric neuronal precursors, which also transiently express tyrosine hydroxylase, If this precursor pool is el iminated in vitro by complement-mediated lysis, enteric neurons contin ue to develop; however, none of these are serotonergic. In the mouse, the Mash-1(-/-) mutation, which eliminates sympathetic neurons, also p revents the development of enteric serotonergic neurons, Other enteric neuronal populations, however, including those that contain calcitoni n gene related peptide are present, Enteric tyrosine hydroxylase-conta ining cells co-express Mash-1 and are eliminated by the Mash-1(-/-) mu tation, consistent with the idea that in the mouse, as in the rat, the se 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 sugges t that enteric neurons are derived from at least two progenitor lineag es, One transiently expresses sympathoadrenal markers, is Mash-1-depen dent, and generates early-born enteric neurons, some of which are sero tonergic, The other is Mash-1-independent, does not express sympathoad renal markers, and generates late-born enteric neurons, some of which contain calcitonin gene related peptide.