Expression patterns of basic helix-loop-helix transcription factors define subsets of olfactory progenitor cells

Expression patterns of basic helix-loop-helix transcription factors define subsets of olfactory progenitor cells
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DOI:
10.1002/cne.20316
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发表时间:
2004-11-08
影响因子:
2.5
通讯作者:
Schwob, JE
Schwob, JE
中科院分区:
医学3区
文献类型:
--
作者:
Manglapus, GL;Youngentob, SL;Schwob, JE

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吸入嗅毒素甲基溴对嗅上皮的直接损伤激活了多能球状基底细胞群,这些细胞群重新构成所有耗尽的细胞群。因为已知基本螺旋-环-螺旋转录因子家族的成员调节神经发生和细胞产生,所以我们进行原位杂交以检查甲基溴损伤后大鼠嗅上皮恢复期间该家族的几个成员的表达。表达前神经转录激活因子Mash 1、Neurogenin 1和NeuroD的基底细胞数量在损伤后1天急剧下降。Mash 1水平在2天后开始恢复,Neurogenin 1和NeuroD在3天后恢复,大量神经元在4天后重新出现。抗神经发生因子Hes 1仅限于未损伤的嗅上皮的支持细胞和相邻的呼吸上皮。溴甲烷损伤后立即,但不是在球切除术后的任何时间,大部分残留的,标记物确认的球状基底细胞启动Hes 1的表达。随后,Hes 1阳性细胞失去与基底层的联系,向顶部移动,并分化为支持细胞。与此相反,Hes 5表达的一个小的球状基底细胞和嗅鞘神经胶质细胞在正常粘膜; Hes 5标签消失,从这两个短暂的病变后。总之,外周损伤后神经元群体的恢复再现了上皮细胞胚胎发育过程中观察到的转录因子表达序列。Hes 1的表达标志着溴甲烷损伤后球状基底细胞群定向分化为支持细胞。(C)2004 Wiley-Liss,Inc.
Direct damage to the olfactory epithelium by inhalation of the olfactotoxin methyl bromide activates a population of multipotent globose basal cells, which reconstitute all depleted cell populations. Because members of the basic helix-loop-helix family of transcription factors are known to regulate neurogenesis and cell production, we performed in situ hybridization to examine the expression of several members of that family during the recovery of the rat olfactory epithelium after methyl bromide lesion. The numbers of basal cells expressing the proneural transcriptional activators Mash1, Neurogenin1, and NeuroD all fall precipitously 1 day after lesion. Mash1 levels begin to recover by 2 days, Neurogenin1 and NeuroD by 3 days, and substantial numbers of neurons reappear by 4 days. The antineurogenic factor Hes1 is limited to the sustentacular cells of the unlesioned olfactory epithelium and to the adjoining respiratory epithelium. Immediately after methyl bromide lesion, but not at any time after bulbectomy, a large fraction of residual, marker-confirmed globose basal cells initiate expression of Hes1. Subsequently, the Hes1-positive cells lose their association with the basal lamina, shift apically, and differentiate into sustentacular cells. In contrast, Hes5 is expressed by a small subset of globose basal cells and by olfactory ensheathing glia in the normal mucosa; Hes5 label disappears from both transiently after lesion. In sum, the recovery of the neuronal population after peripheral lesion recapitulates the sequence of transcription factor expression observed during embryonic development of the epithelium. Moreover, expression of Hes1 marks that population of globose basal cells committed to making sustentacular cells after methyl bromide lesion. (C) 2004 Wiley-Liss, Inc.