Doublesex and mab-3-related transcription factor 5 promotes midbrain dopaminergic identity in pluripotent stem cells by enforcing a ventral-medial progenitor fate

被引：34

作者：

Gennet, Nicole ^{[1
]}

Gale, Emily ^{[1
]}

Nan, Xinsheng ^{[1
]}

Farley, Emma ^{[1
]}

Takacs, Katalin ^{[1
]}

Oberwallner, Barbara ^{[1
]}

Chambers, David ^{[2
]}

Li, Meng ^{[1
]}

机构：

[1] Univ London Imperial Coll Sci Technol & Med, Med Res Council Clin Sci Ctr, Fac Med, London W12 0NN, England

[2] Kings Coll London, Med Res Council Ctr Dev Neurobiol, London SE1 1UL, England

来源：

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA | 2011年 / 108卷 / 22期

基金：

英国医学研究理事会;

关键词：

NEURON DEVELOPMENT; SPECIFICATION; GENE; DIFFERENTIATION; NEUROGENESIS; GENERATION; SYSTEM; PLATE; PITX3; MICE;

D O I：

10.1073/pnas.1016679108

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

Understanding the control of cell-fate choices during embryonic stem cell (ESC) differentiation is crucial for harnessing strategies for efficient production of desired cell types for pharmaceutical drug screening and cell transplantation. Here we report the identification of the zinc finger-like doublesex and mab-3-related transcription factor 5 (Dmrt5) as a marker for mammalian ventral-medial mesencephalic neuroepithelium that give rise to dopamine neurons. Gain-and loss-of-function studies in ESC demonstrate that Dmrt5 is critically involved in the specification of ventral-medial neural progenitor cell fate and the subsequent generation of dopamine neurons expressing essential midbrain characteristics. Genome-wide analysis of Dmrt5-mediated transcriptome changes and expression profiling of ventral-medial and ventral-lateral mesencephalic neuroepithelium revealed suppressive and inductive regulatory roles for Dmrt5 in the transcription program associated with the ventral-medial neural progenitor fates. Together, these data identify Dmrt5 as an important player in ventral mesencephalic neural fate specification.

引用

页码：9131 / 9136

页数：6

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