Distinct roles of hand2 in developing and adult autonomic neurons
Distinct roles of hand2 in developing and adult autonomic neurons
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DOI：
10.1002/dneu.22378
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发表时间：
2016-10
影响因子：
3
通讯作者：
Sabine Stanzel;J. Stubbusch;Abhijeet Pataskar;M. Howard;T. Deller;U. Ernsberger;V. Tiwari;H. Rohrer;Konstantina Tsarovina
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文献类型：
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作者：
Sabine Stanzel;J. Stubbusch;Abhijeet Pataskar;M. Howard;T. Deller;U. Ernsberger;V. Tiwari;H. Rohrer;Konstantina Tsarovina
BHLH转录因子Hand2对胚胎交感神经元去甲肾上腺素能特性的获得和维持至关重要，并控制神经母细胞的增殖。Hand2也在胚胎和出生后的副交感神经节中表达，并在交感神经元中持续表达，直到成年期。在这里，我们讨论它在副交感神经元和成年交感神经元发育中的作用。我们利用副交感神经节中瞬时表达的DBH，通过与DbhiCre转基因小鼠杂交，有条件地删除了副交感蝶腭神经节中的Hand2基因。与交感神经节相比，消除Hand2对E12.5和E16.5的胸径和蝶腭神经节大小没有影响。这些发现显示了Hand2在副交感和交感神经谱系中的不同功能。我们先前在鸡有丝分裂后分化的交感神经元中敲除Hand2导致去甲肾上腺素能标志基因表达减少，但尚不清楚在成年动物中是否需要Hand2来维持去甲肾上腺素能神经元的特性。我们现在表明，与发育过程中的情况相反，在表达DBH的成年交感神经元中消除Hand2并不会减少Th和DBH的表达。然而，成年交感神经元的基因表达谱确定了75个依赖于Hand2的靶基因。有趣的是，相当大比例的下调基因(15%)编码具有突触和神经传递功能的蛋白质。这些结果表明，在交感神经元成熟过程中，Hand2靶基因发生了变化。虽然Hand2在发育过程中控制着调节去甲肾上腺素能分化的基因，但Hand2似乎参与了控制成年交感神经元神经传递的基因的调节。©2016 Wiley期刊，Inc.开发神经生物学76：1111-1124,2016
The bHLH transcription factor Hand2 is essential for the acquisition and maintenance of noradrenergic properties of embryonic sympathetic neurons and controls neuroblast proliferation. Hand2 is also expressed in embryonic and postnatal parasympathetic ganglia and remains expressed in sympathetic neurons up to the adult stage. Here, we address its function in developing parasympathetic and adult sympathetic neurons. We conditionally deleted Hand2 in the parasympathetic sphenopalatine ganglion by crossing a line of floxed Hand2 mice with DbhiCre transgenic mice, taking advantage of the transient Dbh expression in parasympathetic ganglia. Hand2 elimination does not affect Dbh expression and sphenopalatine ganglion size at E12.5 and E16.5, in contrast to sympathetic ganglia. These findings demonstrate different functions for Hand2 in the parasympathetic and sympathetic lineage. Our previous Hand2 knockdown in postmitotic, differentiated chick sympathetic neurons resulted in decreased expression of noradrenergic marker genes but it was unclear whether Hand2 is required for maintaining noradrenergic neuron identity in adult animals. We now show that Hand2 elimination in adult Dbh‐expressing sympathetic neurons does not decrease the expression of Th and Dbh, in contrast to the situation during development. However, gene expression profiling of adult sympathetic neurons identified 75 Hand2‐dependent target genes. Interestingly, a notable proportion of down‐regulated genes (15%) encode for proteins with synaptic and neurotransmission functions. These results demonstrate a change in Hand2 target genes during maturation of sympathetic neurons. Whereas Hand2 controls genes regulating noradrenergic differentiation during development, Hand2 seems to be involved in the regulation of genes controlling neurotransmission in adult sympathetic neurons. © 2016 Wiley Periodicals, Inc. Develop Neurobiol 76: 1111–1124, 2016