Expression of Ret-, p75(NTR)-, Phox2a-, Phox2b-, and tyrosine hydroxylase-immunoreactivity by undifferentiated neural crest-derived cells and different classes of enteric neurons in the embryonic mouse gut

Cells of the enteric nervous system are derived from the neural crest. Prob es to a number of molecules identify neural crest-derived cells within the gastrointestinal tract of embryonic mice prior to their differentiation int o neurons and glial cells. However, it is unclear whether the different mar kers are identifying all neural crest-derived cells, In this study the dist ribution of p75(NTR)-immunoreactivity was compared with that of Ret-, Phox2 a-, Phox2b-, and tyrosine hydroxylase (TH) in undifferentiated neural crest -derived cells in the E10.5-E13.5 mouse intestine. Neural crest-derived cel ls colonise the embryonic mouse gut in a rostral-to-caudal wave between E9. 5-E14, and differentiation into enteric neurons also occurs in a rostral-to -caudal wave. Thus, the most caudal neural crest-derived cells within the g ut are undifferentiated, These most caudal neural crest-derived cells co-ex pressed p75(NTR)-, Phox2b- and Ret-immunoreactivity; at E10.5 a sub-populat ion was also TH-positive, The most caudal cells did not show Phox2a-immunor eactivity at any stage. However, a sub-population of cells, which was rostr al to the undifferentiated neural crest-derived cells, was Phox2a-positive, and these are likely to be cells beginning to differentiate along a neuron al lineage. The expression of Ret-, Phox2a-, Phox2b- and p75(NTR)-immunorea ctivity by two classes of enteric neurons that differentiate prior to birth was also examined. Nitric oxide synthase (NOS) neurons showed Phox2b and R et immunoreactivity at all ages, and Phox2a and p75(NTR) immunoreactivity o nly transiently. Calcitonin gene-related peptide (CGRP) neurons showed Phox 2b and Ret-immunoreactivity, but not Phox2a immunoreactivity. It is conclud ed that all undifferentiated neural crest-derived cells initially express P hox2b, Pet, and p75(NTR); a Subpopulation of these cells also expresses TH transiently, Those cells that are beginning to differentiate along a neuron al lineage maintain their expression of Phox2b and Ret, and they start to e xpress Phox2a, but down-regulate p75(NTR); those cells that differentiate a long a glial lineage downregulate Pet and maintain their expression of p75( NTR). Dev Dyn 1999;216:137-152, (C) 1999 Wiley-Liss, Inc.