Prox1 postmitotically defines dentate gyrus cells by specifying granule cell identity over CA3 pyramidal cell fate in the hippocampus

被引:117
作者
Iwano, Tomohiko [1 ]
Masuda, Aki [1 ]
Kiyonari, Hiroshi [2 ]
Enomoto, Hideki [3 ]
Matsuzaki, Fumio [1 ]
机构
[1] RIKEN Ctr Dev Biol, Lab Cell Asymmetry, Chuou Ku, Kobe, Hyogo 6500047, Japan
[2] RIKEN Ctr Dev Biol, Lab Anim Resources & Genet Engn, Chuou Ku, Kobe, Hyogo 6500047, Japan
[3] RIKEN Ctr Dev Biol, Lab Neuronal Differentiat & Regenerat, Chuou Ku, Kobe, Hyogo 6500047, Japan
来源
DEVELOPMENT | 2012年 / 139卷 / 16期
关键词
Prox1; Cell fate determination; Dentate gyrus granule cell; CA3 pyramidal cell; Mouse; ADULT NEUROGENESIS; MOUSE FOREBRAIN; GENE-TRANSFER; EXPRESSION; BRAIN; NEURONS; DIFFERENTIATION; PROTEINS; MICE; ZONE;
D O I
10.1242/dev.080002
中图分类号
Q [生物科学];
学科分类号
07 ; 0710 ; 09 ;
摘要
The brain is composed of diverse types of neurons that fulfill distinct roles in neuronal circuits, as manifested by the hippocampus, where pyramidal neurons and granule cells constitute functionally distinct domains: cornu ammonis (CA) and dentate gyrus (DG), respectively. Little is known about how these two types of neuron differentiate during hippocampal development, although a set of transcription factors that is expressed in progenitor cells is known to be required for the survival of granule cells. Here, we demonstrate in mice that Prox1, a transcription factor constitutively expressed in the granule cell lineage, postmitotically functions to specify DG granule cell identity. Postmitotic elimination of Prox1 caused immature DG neurons to lose the granule cell identity and in turn terminally differentiate into the pyramidal cell type manifesting CA3 neuronal identity. By contrast, Prox1 overexpression caused opposing effects on presumptive hippocampal pyramidal cells. These results indicate that the immature DG cell has the potential to become a granule cell or a pyramidal cell, and Prox1 defines the granule cell identity. This bi-potency is lost in mature DG cells, although Prox1 is still required for correct gene expression in DG granule cells. Thus, our data indicate that Prox1 acts as a postmitotic cell fate determinant for DG granule cells over the CA3 pyramidal cell fate and is crucial for maintenance of the granule cell identity throughout the life.
引用
收藏
页码:3051 / 3062
页数:12
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