Elsevier

Developmental Biology

Volume 204, Issue 2, 15 December 1998, Pages 385-406
Developmental Biology

Regular Article
Age-Dependent Differences in the Effects of GDNF and NT-3 on the Development of Neurons and Glia from Neural Crest-Derived Precursors Immunoselected from the Fetal Rat Gut: Expression of GFRα-1in Vitroandin Vivo

https://doi.org/10.1006/dbio.1998.9090Get rights and content
Under a Creative Commons license
open archive

Abstract

No enteric neurons or glia develop in the gut below the rostral foregut in mice lacking glial cell line-derived neurotrophic factor (GDNF) or Ret. We analyzed the nature and age dependence of the effects of GDNF and, for comparison, those of NT-3, on thein vitrodevelopment of the precursors of enteric neurons and glia. Positive and negative immunoselection with antibodies to p75NTRwere used to isolate crest-derived and crest-depleted populations of cells from the fetal rat bowel at E12, 14, and 16. Cells were typed immunocytochemically. GDNF stimulated the proliferation of nestin-expressing precursor cells isolated at E12, but not at E14–16. GDNF promoted the development of peripherin-expressing neurons (E12 ⪢ E14–16) and expression of TrkC. GDNF inhibited expression of S-100-expressing glia at E14–16. NT-3 did not affect cells isolated at E12, never stimulated precursors to proliferate, and promoted glial as well as neuronal development at E14–16. GFRα-1 was expressed both by crest- and non-crest-derived cells, although only crest-derived cells anchored GFRα-1 and GFRα-2 (GFRα-1 ⪢ GFRα-2). GDNF increased the number of neurons anchoring GFRα-1. GFRα-1 is immunocytochemically detectable in neurons of the E13 intestine and persists in adult neurons of both plexuses. We suggest that GDNF stimulates the proliferation of an early (E12) NT-3-insensitive precursor common to enteric neurons and glia; by E14, this common precursor is replaced by specified NT-3-responsive neuronal and glial progenitors. GDNF exerts a neurotrophic, but not a mitogenic, effect on the neuronal progenitor. The glial progenitor is not maintained by GDNF.

Keywords

neural crest
enteric nervous system
gut
intestine
GDNF
Ret
GFRα-1
GFRα-2
NT-3
TrkC
nestin
PCNA
Hirschsprung's disease

Cited by (0)

J. W. PollardJ. M. Walker

1

To whom correspondence should be addressed. 630 W, 168th Street, New York, NY 10032. Fax: 212-305-3970. E-mail:[email protected].