Sequential requirement of Sox4 and Sox11 during development of the sympathetic nervous system
Sequential requirement of Sox4 and Sox11 during development of the sympathetic nervous system
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DOI：
10.1242/dev.042101
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发表时间：
2010-03-01
期刊：
影响因子：
4.6
通讯作者：
Sock, Elisabeth
中科院分区：
文献类型：
--
作者：
Potzner, Michaela R.;Tsarovina, Konstantina;Sock, Elisabeth
高度相关的转录因子Sox 4和Sox 11在发育中的交感神经系统中表达。在小鼠中，Sox 11首先出现，而Sox 4则较晚出现。使用小鼠突变和过表达策略在鸡，我们研究了这两个SoxC蛋白在这个组织中的作用。Sox4和Sox11主要通过促进交感神经元的泛神经元或去甲肾上腺素能分化发挥作用，这可能是从中枢神经系统神经元前体的研究中所预期的。调节交感神经元分化的转录网络保持完整，去甲肾上腺素能标记物的表达仅显示出微小的改变。相反，Sox11需要在早期交感神经节的酪氨酸羟化酶表达细胞的增殖，而Sox4确保这些细胞在后期阶段的生存。在缺乏Sox4和Sox11的情况下，由于连续的增殖和存活缺陷，交感神经节在整个胚胎发生过程中保持发育不良。因此，交感神经节在成人中是基本的，并且靶组织的交感神经支配受损，导致严重的自主神经功能障碍。
The highly related transcription factors Sox4 and Sox11 are expressed in the developing sympathetic nervous system. In the mouse, Sox11 appears first, whereas Sox4 is prevalent later. Using mouse mutagenesis and overexpression strategies in chicken, we studied the role of both SoxC proteins in this tissue. Neither Sox4 nor Sox11 predominantly functioned by promoting pan-neuronal or noradrenergic differentiation of sympathetic neurons as might have been expected from studies in neuronal precursors of the central nervous system. The transcriptional network that regulates the differentiation of sympathetic neurons remained intact and expression of noradrenergic markers showed only minor alterations. Instead, Sox11 was required in early sympathetic ganglia for proliferation of tyrosine hydroxylase-expressing cells, whereas Sox4 ensured the survival of these cells at later stages. In the absence of both Sox4 and Sox11, sympathetic ganglia remained hypoplastic throughout embryogenesis because of consecutive proliferation and survival defects. As a consequence, sympathetic ganglia were rudimentary in the adult and sympathetic innervation of target tissues was impaired leading to severe dysautonomia.