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-1 in vitro and in vivo
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-1 in vitro and in vivo
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DOI：
10.1006/dbio.1998.9090
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发表时间：
1998-12-15
影响因子：
2.7
通讯作者：
Gershon, MD
中科院分区：
文献类型：
--
作者：
Chalazonitis, A;Rothman, TP;Gershon, MD
在缺乏神经胶质细胞系衍生神经营养因子（GDNF）或Ret的小鼠中，鼻侧前肠以下的肠道中没有肠神经元或胶质细胞发育。我们分析了GDNF和NT-3对肠神经元和胶质细胞前体体外发育的影响的性质和年龄依赖性，并进行了比较。采用p75（NTR）抗体进行阳性和阴性免疫选择，分别在E12、14和16时从胎鼠肠中分离出波峰来源和波峰枯竭的细胞群。细胞免疫细胞化学分型。GDNF刺激了E12分离的表达巢蛋白的前细胞的增殖，而E14-16则没有。GDNF促进表达外周蛋白的神经元的发育（E12远高于E14-16）和TrkC的表达。GDNF抑制表达s -100的胶质细胞在E14-16的表达。NT-3不影响E12分离的细胞，从不刺激前体增殖，并促进E14-16的神经胶质和神经元发育。冠源性细胞和非冠源性细胞均表达GFR α -1，尽管只有冠源性细胞锚定GFR α -1和GFR α -2 （GFR α -1远高于GFR α -2）。GDNF增加了锚定GFR α -1的神经元数量。GFR α -1在E13肠的神经元中可被免疫细胞化学检测到，并在两神经丛的成年神经元中持续存在。我们认为GDNF刺激肠神经元和胶质细胞常见的早期（E12） nt -3不敏感前体的增殖；到E14时，这种共同前体被特定的nt -3反应神经元和胶质祖细胞所取代。GDNF对神经元祖细胞具有神经营养作用，但不具有有丝分裂作用。胶质祖细胞不受GDNF的维持。(C) 1998学术出版社。
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 the in vitro development of the precursors of enteric neurons and glia. Positive and negative immunoselection with antibodies to p75(NTR) were 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 much greater than 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. GFR alpha-1 was expressed both by crest- and non-crest-derived cells, although only crest-derived cells anchored GFR alpha-1 and GFR alpha-2 (GFR alpha-1 much greater than GFR alpha-2). GDNF increased the number of neurons anchoring GFR alpha-1. GFR alpha-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. (C) 1998 Academic Press.