Koo Hei Yeun, Oh Jae Hwan, Durán Alonso María Beatriz, Hernández Iris López, González-Vallinas Margarita, Alonso María Teresa, Tena Juan J, Gil-Gálvez Alejandro, Giraldez Fernando, Bok Jinwoong, Schimmang Thomas
Department of Anatomy, Yonsei University College of Medicine, Seoul, South Korea.
Brain Korea 21 Project for Medical Science, Yonsei University College of Medicine, Seoul, South Korea.
Dev Dyn. 2025 Apr;254(4):365-372. doi: 10.1002/dvdy.747. Epub 2024 Oct 1.
The mechanisms underlying the formation of complex structures such as during the outgrowth of the cochlear duct are still poorly understood.
We have analyzed the morphological and molecular changes associated with cochlear development in mouse mutants for the transcription factor Meis2, which show defective coiling of the cochlea. These morphological abnormalities were accompanied by the formation of ectopic and extra rows of sensory hair cells. Gene profiling of otic vesicles from Meis2 mutants revealed a dysregulation of genes that are potentially involved in Sonic hedgehog (Shh)-mediated patterning of the cochlear duct. Like in Shh mutants, Meis2 defective mice showed a loss of genes that are expressed in the apical part of the cochlear duct.
Taken together, these data reveal that the loss of Meis2 leads to a phenotype that resembles Shh mutants, suggesting that Meis2 is instrumental for cochlear Shh signaling. The modulation of the same subset of genes provides an interesting insight into which Shh responsive genes are essential for outgrowth and patterning of the cochlear duct.
诸如在耳蜗管生长过程中形成复杂结构的潜在机制仍知之甚少。
我们分析了转录因子Meis2基因敲除小鼠耳蜗发育过程中的形态学和分子变化，这些小鼠表现出耳蜗卷曲缺陷。这些形态学异常伴随着异位和额外排的感觉毛细胞的形成。对Meis2基因敲除小鼠耳泡的基因谱分析揭示了可能参与声波刺猬因子（Shh）介导的耳蜗管模式形成的基因失调。与Shh基因敲除小鼠一样，Meis2缺陷小鼠耳蜗管顶端表达的基因缺失。
综上所述，这些数据表明Meis2缺失导致的表型类似于Shh基因敲除小鼠，提示Meis2对耳蜗Shh信号传导起作用。对同一组基因的调控为了解哪些Shh反应性基因对耳蜗管的生长和模式形成至关重要提供了有趣的见解。
