Beijing Key Laboratory of Gene Resource and Molecular Development, Beijing Normal University, Beijing, 100875, China.
College of Life Sciences, Hainan Normal University, Haikou, 571158, China.
Dev Neurobiol. 2018 Jan;78(1):15-38. doi: 10.1002/dneu.22551. Epub 2017 Nov 17.
Song control nuclei have distinct sexual differences in songbirds. However, the mechanism that underlies the sexual differentiation of song nuclei is still not well understood. Using a combination of anatomical, pharmacological, genetic, and behavioral approaches, the present study investigated the role of erbb2 (a homolog of the avian erythroblastic leukemia viral oncogene homolog 2) and the erbb2-interacting gene, erbin, in the sexual differentiation of the song nucleus HVC in the Bengalese finch. We first found that both erbin and erbb2 were expressed in the developing HVC at posthatch day (PHD) 15 in a male-biased fashion using qRT-PCR and in situ hybridization. Following the addition of a pharmaceutical inhibitor of the ErbB2 signaling pathway to the culture medium, cell proliferation in the cultured ventricle zone (VZ) that overlies the developing HVC decreased significantly. After the injection of erbin- or erbb2-interfering lentiviruses into the HVC and its overlying VZ at PHD 15, the cell proliferation in the VZ at PHD 24, the number of the differentiated neurons (Hu /BrdU or NeuN /BrdU ) in the HVC at PHD 31 or PHD 130, and the number of RA-projecting cells at PHD 130 all decreased significantly. Additionally, the adult songs displayed serious abnormalities. Finally, 173 male-biased genes were expressed in the developing HVC at PHD 15 using cDNA microarrays, of which 27.2% were Z-linked genes and approximately 20 genes were involved in the Erbin- or ErbB2-related signaling pathways. Our results provide some specific genetic factors that contribute to neurogenesis and sex differentiation in a song nucleus of songbirds. © 2017 Wiley Periodicals, Inc. Develop Neurobiol 78: 15-38, 2018.
鸣禽的 song control 核具有明显的性别差异。然而，song 核性别分化的机制仍不清楚。本研究采用解剖学、药理学、遗传学和行为学相结合的方法，研究了 erbb2（禽红细胞白血病病毒致癌基因同源物 2 的同源物）和 erbb2 相互作用基因 erbin 在雄性伯尔尼雀 HVC 中 song 核的性别分化中的作用。我们首先发现，qRT-PCR 和原位杂交结果均显示，在孵化后第 15 天（PHD15），erbin 和 erbb2 均以雄性偏倚的方式在发育中的 HVC 中表达。在培养基中添加 ErbB2 信号通路的药物抑制剂后，覆盖发育中的 HVC 的培养室（VZ）中的细胞增殖明显减少。在 PHD15 时将 erbin 或 erbb2 干扰慢病毒注入 HVC 及其覆盖的 VZ 后，VZ 中的细胞增殖在 PHD24 时显著减少，PHD31 或 PHD130 时 HVC 中的分化神经元（Hu/BrdU 或 NeuN/BrdU）数量和 PHD130 时 RA 投射细胞的数量均显著减少。此外，成年 song 也显示出严重的异常。最后，使用 cDNA 微阵列在 PHD15 时在发育中的 HVC 中表达了 173 个雄性偏倚基因，其中 27.2%是 Z 连锁基因，约 20 个基因涉及 Erbin 或 ErbB2 相关信号通路。我们的研究结果为鸟类 song 核中的神经发生和性别分化提供了一些特定的遗传因素。
