Unique expression patterns of cell fate molecules delineate sequential stages of dentate gyrus development

Unique expression patterns of cell fate molecules delineate sequential stages of dentate gyrus development
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DOI:
10.1523/jneurosci.20-16-06095.2000
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发表时间:
2000-08-15
影响因子:
5.3
通讯作者:
Lowenstein, DH
Lowenstein, DH
中科院分区:
医学1区
文献类型:
--
作者:
Pleasure, SJ;Collins, AE;Lowenstein, DH

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海马的齿状回是独特的组织与移位增殖区,继续产生齿状颗粒细胞在整个生命。我们分析了齿状回发育过程中Notch受体、Notch配体和基本螺旋-环-螺旋(bHLH)基因的表达,以确定维持未分化前体池的需求是否反映在这些基因的表达模式中。这些基因中的许多在胚胎第16和17天在大鼠皮层神经上皮中弥漫性表达,就在新生颗粒细胞和齿状前体细胞迁移到齿状原体之前。然而,此时,Mash1、Math3和Id3的表达都集中在特异性产生颗粒细胞和齿状前体细胞的区域。2天后,在第一颗粒细胞和齿状前体细胞迁移时,在从室下区向发育中的齿状回迁移的路线上可见表达Mash1的细胞。新生颗粒细胞表达NeuroD也存在于这一迁移途径中。在出生后的第一周,表达Mash1的前体细胞位于齿状颗粒细胞门部,到出生后的第三周,它们大部分在齿状颗粒细胞层门侧的亚颗粒区占据最终位置。末梢分化后,出生在肝门区或亚颗粒区的颗粒细胞开始表达NeuroD,随后表达NeuroD2。本研究证实bHLH mrna的表达模式在齿状回形成过程中发生了进化,并且位于成熟齿状回中的前体细胞与发育过程中发现的前体细胞具有共同的特征。因此,许多已知的调节其他脑区细胞命运和前体池大小的相同机制可能在齿状回发育的所有阶段都起作用。
The dentate gyrus of the hippocampus is uniquely organized with a displaced proliferative zone that continues to generate dentate granule cells throughout life. We have analyzed the expression of Notch receptors, Notch ligands, and basic helix-loop-helix (bHLH) genes during dentate gyrus development to determine whether the need to maintain a pool of undifferentiated precursors is reflected in the patterns of expression of these genes. Many of these genes are expressed diffusely throughout the cortical neuroepithelium at embryonic days 16 and 17 in the rat, just preceding the migration of newly born granule cells and dentate precursor cells into the dentate anlage. However, at this time, Mash1, Math3, and Id3 expression are all concentrated in the area that specifically gives rise to granule cells and dentate precursor cells. Two days later, at the time of migration of the first granule cells and dentate precursor cells, cells expressing Mash1 are seen in the migratory route from the subventricular zone to the developing dentate gyrus. Newly born granule cells expressing NeuroD are also present in this migratory pathway. In the first postnatal week, precursor cells expressing Mash1 reside in the dentate hilus, and by the third postnatal week they have largely taken up their final position in the subgranular zone along the hilar side of the dentate granule cell layer. After terminal differentiation, granule cells born in the hilus or the subgranular zone begin to express NeuroD followed by NeuroD2. This study establishes that the expression patterns of bHLH mRNAs evolve during the formation of the dentate gyrus, and the precursor cells resident in the mature dentate gyrus share features with precursor cells found in development. Thus, many of the same mechanisms that are known to regulate cell fate and precursor pool size in other brain regions are likely to be operative in the dentate gyrus at all stages of development.