Cell and Tissue Research ( IF 3.2 ) Pub Date : 2023-03-24 , DOI: 10.1007/s00441-023-03763-9 Ali Jason Saleh 1 , Yannis Ahmed 2 , Lars-Oliver Peters 1 , Hans Gerd Nothwang 1, 3, 4
The mammalian and avian auditory brainstem likely arose by independent evolution. To compare the underlying molecular mechanisms, we focused on Atoh7, as its expression pattern in the mammalian hindbrain is restricted to bushy cells in the ventral cochlear nucleus. We thereby took advantage of an Atoh7 centered gene regulatory network (GRN) in the retina including upstream regulators, Hes1 and Pax6, and downstream targets, Ebf3 and Eya2. In situ hybridization demonstrated for the latter four genes broad expression in all three murine cochlear nuclei at postnatal days (P) 4 and P30, contrasting the restricted expression of Atoh7. In chicken, all five transcription factors were expressed in all auditory hindbrain nuclei at embryonic day (E) 13 and P14. Notably, all five genes showed graded expression in the embryonic nucleus magnocellularis (NM). Atoh7 was highly expressed in caudally located neurons, whereas the other four transcription factors were highly expressed in rostrally located neurons. Thus, Atoh7 shows a strikingly different expression between the mammalian and avian auditory hindbrain. This together with the consistent absence of graded expression of GRN components in developing mammalian nuclei provide the first molecular support to the current view of convergent evolution as a major mechanism in the amniote auditory hindbrain. The graded expression of five transcription factors specifically in the developing NM confirms this nucleus as a central organizer of tonotopic features in birds. Finally, the expression of all five retinal GRN components in the auditory system suggests co-options of genes for development of sensory systems of distinct modalities.
中文翻译:
Atoh7基因调控网络在小鼠和鸡听觉后脑中的比较表达分析
哺乳动物和鸟类的听觉脑干可能是通过独立进化产生的。为了比较潜在的分子机制,我们专注于Atoh7,因为它在哺乳动物后脑中的表达模式仅限于腹侧耳蜗核中的浓密细胞。因此,我们利用了视网膜中以Atoh7为中心的基因调控网络 (GRN),包括上游调节因子Hes1和Pax6,以及下游靶标Ebf3和Eya2。原位杂交证明后四种基因在出生后第 4 天和第 30 天在所有三个小鼠耳蜗核中广泛表达,与 Atoh7 的受限表达形成对比. 在鸡中,所有五种转录因子在胚胎第 (E) 13 天和第 14 天的所有听觉后脑细胞核中均有表达。值得注意的是,所有五个基因在胚胎大细胞核 (NM) 中均显示出分级表达。Atoh7在位于尾部的神经元中高度表达,而其他四种转录因子在位于喙部的神经元中高度表达。因此,Atoh7显示出哺乳动物和鸟类听觉后脑之间截然不同的表达。这与发育中的哺乳动物细胞核中 GRN 成分的分级表达的一致缺失一起,为目前认为趋同进化作为羊膜动物听觉后脑的主要机制的观点提供了第一个分子支持。五种转录因子在发育中的 NM 中的分级表达证实了该细胞核是鸟类紧张性特征的中心组织者。最后,听觉系统中所有五个视网膜 GRN 成分的表达表明基因的共同选择,用于开发不同模式的感觉系统。