Details

Autor(en) / Beteiligte

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

Titel

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

Ist Teil von

• Neuron (Cambridge, Mass.), 2003-12, Vol.40 (5), p.917-929

Ort / Verlag

United States: Elsevier Inc

Erscheinungsjahr

2003

Link zum Volltext

Quelle

MEDLINE

Beschreibungen/Notizen

• 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 Ednrb sl/sl gut, where they engrafted and formed neurons as efficiently as in the wild-type gut.