The basic helix-loop-helix factor Hand2 regulates autonomic nervous system development
The basic helix-loop-helix factor Hand2 regulates autonomic nervous system development
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DOI：
10.1002/dvdy.20544
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发表时间：
2005-11-01
影响因子：
2.5
通讯作者：
Cserjesi, P
中科院分区：
文献类型：
--
作者：
Morikawa, Y;Dai, YS;Cserjesi, P
哺乳动物自主神经系统（ANS）的发育需要许多转录因子的组合作用，包括Mash1、Phox2b和GATA3。我们发现bHLH转录因子Hand2 （dHAND）在交感神经系统（SNS）发育过程中与Mash1同时表达，并且Hand2的表达不依赖于Mash1。这表明这两个bHLH因素在社交网络的发展过程中是并行的。我们还发现，Hand2的异位表达激活了P19胚胎癌细胞的神经元程序，并促进了一种与周围神经元（包括SNS谱系的神经元）相对应的表型的获得。我们提出Hand2与转录网络的其他成员并行调节ANS的发育，但可以通过包括激活Mashl在内的交叉调控机制异位激活该程序。我们发现这种功能依赖于它与组蛋白乙酰转移酶p300/CBP的相互作用，表明Hand2作为一个更大的转录复合体的一部分促进了ANS的发育。
Mammalian autonomic nervous system (ANS) development requires the combinatorial action of a number of transcription factors, which include Mash1, Phox2b, and GATA3. Here we show that the bHLH transcription factor, Hand2 (dHAND), is expressed concurrently with Mash1 during sympathetic nervous system (SNS) development and that the expression of Hand2 is not dependent on Mashl. This suggests that these two bHLH factors work in parallel during SNS development. We also show that ectopic expression of Hand2 activates the neuronal program and promotes the acquisition of a phenotype corresponding to peripheral neurons including neurons of the SNS lineage in P19 embryonic carcinoma cells. We propose that Hand2 works in parallel with other members of the transcriptional network to regulate ANS developmental but can ectopically activate the program by a cross-regulatory mechanism that includes the activation of Mashl. We show that this function is dependent on its interaction with the histone acetyltransferase p300/CBP, indicating that Hand2 functions to promote ANS development as part of a larger transcriptional complex.