Division of Molecular and Cellular Neuroscience, Institute of Cell Biology and Neuroscience (IBCN)-CONICET, School of Medicine. University of Buenos Aires (UBA), Buenos Aires, Argentina.
Cereb Cortex. 2018 Jan 1;28(1):236-249. doi: 10.1093/cercor/bhw372.
The proper formation and morphogenesis of dendrites is essential to the establishment of neuronal connectivity. We report that 2 members of the Pea3 family of transcription factors, Etv4 and Etv5, are expressed in hippocampal neurons during the main period of dendritogenesis, suggesting that they have a function in dendrite development. Here, we show that these transcription factors are physiological regulators of growth and arborization of pyramidal cell dendrites in the developing hippocampus. Gain and loss of function assays indicate that Etv4 and Etv5 are required for proper development of hippocampal dendritic arbors and spines. We have found that in vivo deletion of either Etv4 or Etv5 in hippocampal neurons causes deficits in dendrite size and complexity, which are associated with impaired cognitive function. Additionally, our data support the idea that Etv4 and Etv5 are part of a brain-derived neurotrophic factor-mediated transcriptional program required for proper hippocampal dendrite connectivity and plasticity.
树突的正确形成和形态发生对于神经元连接的建立至关重要。我们报告说，Pea3 转录因子家族的 2 个成员，Etv4 和 Etv5，在树突发生的主要时期在海马神经元中表达，这表明它们在树突发育中有功能。在这里，我们表明这些转录因子是发育中海马锥体神经元树突生长和分支的生理调节剂。获得和丧失功能的实验表明，Etv4 和 Etv5 是海马树突分支和棘突正常发育所必需的。我们发现，在海马神经元中体内敲除 Etv4 或 Etv5 会导致树突大小和复杂性的缺陷，这与认知功能受损有关。此外，我们的数据支持这样的观点，即 Etv4 和 Etv5 是脑源性神经营养因子介导的转录程序的一部分，该程序对于海马树突连接和可塑性的正常发挥是必需的。
