@article{7fe773f8703c47ada6b66aa70468cf4e,
title = "Temporally Distinct Requirements for Endothelin Receptor B in the Generation and Migration of Gut Neural Crest Stem Cells",
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.",
author = "Kruger, {Genevieve M.} and Mosher, {Jack T.} and Tsai, {Yu Hwai} and Yeager, {Kelly J.} and Toshihide Iwashita and Gariepy, {Cheryl E.} and Morrison, {Sean J.}",
note = "Funding Information: This work was supported by the Howard Hughes Medical Institute, a Predoctoral Fellowship to G.M.K. from the University of Michigan Institute of Gerontology (AG00114-18), a postdoctoral fellowship to J.T.M. from the UM Cancer Biology Training Program (T32 CA09676), a Michigan Gastrointestinal Peptide Center Pilot Feasibility Grant (to C.E.G.), and the C.S. Mott Children's Hospital Research Fund (to C.E.G.). Thanks to David Adams, Anne Marie Deslaurier, Mark Kiel, Martin White, and the University of Michigan Flow Cytometry Core Facility for flow cytometry (supported in part by the UM-Comprehensive Cancer NIH CA46592 and UM-Multipurpose Arthritis Center NIH AR20557). Thanks to Elizabeth Smith in the Hybridoma Core Facility for antibody production, supported in part through the Michigan Diabetes Research and Training Center (P60DK-20572) and the Rheumatic Disease Center Core (P30 AR48310). Thanks to E. Sandgren for providing alkaline phosphatase transgenic rats and to Myung Shin and Vassilis Pachnis for discussions and for sharing unpublished data.",
year = "2003",
month = dec,
day = "4",
doi = "10.1016/S0896-6273(03)00727-X",
language = "English (US)",
volume = "40",
pages = "917--929",
journal = "Neuron",
issn = "0896-6273",
publisher = "Cell Press",
number = "5",
}