Temporally distinct requirements for endothelin receptor B in the generation and migration of gut neural crest stem cells
Temporally distinct requirements for endothelin receptor B in the generation and migration of gut neural crest stem cells
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DOI：
10.1016/s0896-6273(03)00727-x
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发表时间：
2003-12-04
期刊：
影响因子：
16.2
通讯作者：
Morrison, SJ
中科院分区：
文献类型：
--
作者：
Kruger, GM;Mosher, JT;Morrison, SJ
Endothelin-3/Endothelin Receptor B(EDNRB)信号的缺失导致远端肠道无神经节细胞增多(先天性巨结肠症)，但尚不清楚它是否主要是维持或迁移神经脊祖细胞所必需的。胚胎12.5天(E12.5)时，EDNRB缺陷的肠道神经脊干细胞(NCSCs)减少到野生型的40%，但随后没有观察到NCSCs的进一步枯竭。未分化的神经干细胞在EDNRB缺陷大鼠胚胎和出生后的整个发育过程中一直存在于近端肠道，但在E12.5之后表现出迁移缺陷，阻止了远端肠道的定植。可能需要EDNRB信号来调节神经脊祖细胞对迁移信号的反应，如胶质细胞系衍生神经营养因子(GDNF)。通过将野生型神经干细胞直接移植到EDNRB(s1/s1)肠道的无神经节区，可以绕过这种迁移缺陷，在那里它们与野生型肠道一样有效地植入和形成神经元。
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.