Temporally Distinct Requirements for Endothelin Receptor B in the Generation and Migration of Gut Neural Crest Stem Cells

Genevieve M. Kruger, Jack T. Mosher, Yu Hwai Tsai, Kelly J. Yeager, Toshihide Iwashita, Cheryl E. Gariepy, Sean J. Morrison

Research output: Contribution to journalArticle

114 Scopus citations

Abstract

Loss of Endothelin-3/Endothelin receptor B (EDNRB) signaling leads to aganglionosis of the distal gut (Hirschsprung's disease), but it is unclear whether it is required primarily for neural crest progenitor maintenance or migration. Ednrb-deficient gut neural crest stem cells (NCSCs) were reduced to 40% of wild-type levels by embryonic day 12.5 (E12.5), but no further depletion of NCSCs was subsequently observed. Undifferentiated NCSCs persisted in the proximal guts of Ednrb-deficient rats throughout fetal and postnatal development but exhibited migration defects after E12.5 that prevented distal gut colonization. EDNRB signaling may be required to modulate the response of neural crest progenitors to migratory cues, such as glial cell line-derived neurotrophic factor (GDNF). This migratory defect could be bypassed by transplanting wild-type NCSCs directly into the aganglionic region of the Ednrbsl/sl gut, where they engrafted and formed neurons as efficiently as in the wild-type gut.

Original languageEnglish (US)
Pages (from-to)917-929
Number of pages13
JournalNeuron
Volume40
Issue number5
DOIs
StatePublished - Dec 4 2003

    Fingerprint

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this