Ldb1 is essential for development of Nkx2.1 lineage derived GABAergic and cholinergic neurons in the telencephalon.
Ldb1 is essential for development of Nkx2.1 lineage derived GABAergic and cholinergic neurons in the telencephalon.
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DOI：
10.1016/j.ydbio.2013.10.010
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发表时间：
2014-01-01
影响因子：
2.7
通讯作者：
Rubenstein, John L. R.
中科院分区：
文献类型：
--
作者：
Zhao, Yangu;Flandin, Pierre;Vogt, Daniel;Blood, Alexander;Hermesz, Edit;Westphal, Heiner;Rubenstein, John L. R.
胚胎小鼠腹侧端脑的祖区产生gaba能神经元和胆碱能神经元。我们之前已经证明，两个lim同源结构域（LIM-HD）转录因子Lhx6和Lhx8位于Nkx2.1的下游，对端脑gaba能和胆碱能神经元的发育至关重要。在这里，我们研究了Ldb1的作用，Ldb1是一种直接结合所有LIM-HD因子的核蛋白，在这些腹端脑源性神经元的发育中。我们发现Ldb1在胚胎发育和成熟神经元的Nkx2.1细胞系中表达。Ldb1的条件缺失会导致腹侧端脑一系列基因的表达缺陷，并严重损害皮层中间神经元从腹侧端脑向切向迁移。与Lhx6或Lhx8突变小鼠的表型相似，Ldb1条件突变小鼠显示出端脑gaba能和胆碱能神经元数量的减少。此外，我们的分析揭示了Ldb1突变体的苍白球和纹状体中parvalbumin阳性神经元的发育缺陷。这些结果证明Ldb1作为Lhx6和Lhx8的转录共调节因子在哺乳动物端脑发育的控制中发挥了重要作用。
The progenitor zones of the embryonic mouse ventral telencephalon give rise to GABAergic and cholinergic neurons. We have shown previously that two LIM-homeodomain (LIM-HD) transcription factors, Lhx6 and Lhx8, that are downstream of Nkx2.1, are critical for the development of telencephalic GABAergic and cholinergic neurons. Here we investigate the role of Ldb1, a nuclear protein that binds directly to all LIM-HD factors, in the development of these ventral telencephalon derived neurons. We show that Ldb1 is expressed in the Nkx2.1 cell lineage during embryonic development and in mature neurons. Conditional deletion of Ldb1 causes defects in the expression of a series of genes in the ventral telencephalon and severe impairment in the tangential migration of cortical interneurons from the ventral telencephalon. Similar to the phenotypes observed in Lhx6 or Lhx8 mutant mice, the Ldb1 conditional mutants show a reduction in the number of both GABAergic and cholinergic neurons in the telencephalon. Furthermore, our analysis reveals defects in the development of the parvalbumin-positive neurons in the globus pallidus and striatum of the Ldb1 mutants. These results provide evidence that Ldb1 plays an essential role as a transcription co-regulator of Lhx6 and Lhx8 in the control of mammalian telencephalon development.
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影响因子：
4.6
作者：
Tzchori, Itai;Day, Timothy F.;Yang, Yingzi
通讯作者：
Yang, Yingzi
影响因子：
3.4
作者：
Fragkouli, A;Hearn, C;Pachnis, V
通讯作者：
Pachnis, V
DOI：
10.1073/pnas.0705464104
发表时间：
2007-08-07
影响因子：
11.1
作者：
Zhao, Yangu;Kwan, Kin-Ming;Westphal, Heiner
通讯作者：
Westphal, Heiner
影响因子：
2.5
作者：
Narkis, Ginat;Tzchori, Itai;Cohen, Tsadok;Holtz, Alex;Wier, Eric;Westphal, Heiner
通讯作者：
Westphal, Heiner
影响因子：
64.5
作者：
Thaler, JP;Lee, SK;Pfaff, SL
通讯作者：
Pfaff, SL