Tissue-specific regulation and function of Grb10 during growth and neuronal commitment
Tissue-specific regulation and function of Grb10 during growth and neuronal commitment
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DOI：
10.1073/pnas.1411254111
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发表时间：
2015-06-02
影响因子：
11.1
通讯作者：
Bartolomei, Marisa S.
中科院分区：
文献类型：
--
作者：
Plasschaert, Robert N.;Bartolomei, Marisa S.
生长因子受体结合蛋白 10 (Grb10) 是一种由印记基因编码的信号接头蛋白，在生长控制、细胞增殖和胰岛素信号传导中发挥作用。此外，Grb10 对于成年小鼠的正常行为至关重要。这些功能与 Grb10 独特的组织特异性印记表达相平行； Grb10 的父本拷贝在神经元子集中表达，而母本拷贝在小鼠的大多数其他成体组织中表达。母本表达与父本表达之间转换的机制仍不清楚，父本表达的 Grb10 在神经元中的作用也不清楚。在这里，我们回顾了最近的工作并提供了有助于理解 Grb10 基因调控和功能的补充数据，特别强调生长和神经元发育。此外，我们还发现，小鼠胚胎干细胞在体外分化为α运动神经元，重现了体内神经元发育过程中观察到的从母本表达到父本表达的转变。我们假设等位基因特异性表达的这种转变与 Grb10 在运动神经元和其他神经元组织中的功能作用有关。
Growth-factor receptor bound protein 10 (Grb10) is a signal adapter protein encoded by an imprinted gene that has roles in growth control, cellular proliferation, and insulin signaling. Additionally, Grb10 is critical for the normal behavior of the adult mouse. These functions are paralleled by Grb10's unique tissue-specific imprinted expression; the paternal copy of Grb10 is expressed in a subset of neurons whereas the maternal copy is expressed in most other adult tissues in the mouse. The mechanism that underlies this switch between maternal and paternal expression is still unclear, as is the role for paternally expressed Grb10 in neurons. Here, we review recent work and present complementary data that contribute to the understanding of Grb10 gene regulation and function, with specific emphasis on growth and neuronal development. Additionally, we show that in vitro differentiation of mouse embryonic stem cells into alpha motor neurons recapitulates the switch from maternal to paternal expression observed during neuronal development in vivo. We postulate that this switch in allele-specific expression is related to the functional role of Grb10 in motor neurons and other neuronal tissues.