McCubbin Ryan A, Auwal Mohammad A, Wang Shengzhou, Zepeda Sarai Alvarez, Sasik Roman, Zeller Robert W, Ross Kelly G, Zayas Ricardo M
Department of Biology, San Diego State University, 5500 Campanile Dr., San Diego, CA 92182 USA.
Center for Computational Biology and Bioinformatics, University of California, San Diego, La Jolla, CA 92093 USA.
bioRxiv. 2025 May 16:2025.05.15.654132. doi: 10.1101/2025.05.15.654132.
POU4 homologs are involved in the development of sensory cell types across diverse species, including cnidarians, ascidians, and mammals. Whether these developmental regulators are reused during adult tissue maintenance and regeneration remains a fundamental question in regenerative biology. Here, we investigate the role of the BRN3/POU4 homolog, (), in the regeneration of mechanosensory neurons. We find that is regulated by the SoxB1 homolog, 2, and is expressed in a distinct population of ciliated sensory cells that detect water flow. Transcriptomic analysis of -deficient planarians reveals enrichment for conserved genes associated with human auditory and vestibular function, suggesting that planarian rheosensory neurons share molecular features with mammalian inner ear hair cells. Expression of these conserved genes is abrogated by RNAi-mediated knockdown of . To determine whether these transcriptional changes had functional consequences for mechanosensory neuron identity or behavior, we next assessed the impact of knockdown on sensory function. RNAi results in impaired mechanosensation in both uninjured and regenerating planarians. Together with the loss of terminal differentiation markers in mechanosensory neurons, these findings identify as a key regulator of mechanosensory neuron identity in planarians and support the idea that conserved sensory specification programs are redeployed during adult tissue regeneration.
POU4同源物参与了包括刺胞动物、海鞘和哺乳动物在内的多种物种中感觉细胞类型的发育。这些发育调节因子在成体组织维持和再生过程中是否被重新利用，仍然是再生生物学中的一个基本问题。在这里，我们研究了BRN3/POU4同源物（）在机械感觉神经元再生中的作用。我们发现它受SoxB1同源物2的调控，并在检测水流的不同群体的纤毛感觉细胞中表达。对缺乏该同源物的涡虫进行转录组分析，发现与人类听觉和前庭功能相关的保守基因富集，这表明涡虫的水流感觉神经元与哺乳动物内耳毛细胞具有共同的分子特征。这些保守基因的表达通过RNAi介导的该同源物敲低而被消除。为了确定这些转录变化是否对机械感觉神经元的特性或行为产生功能影响，我们接下来评估了敲低该同源物对感觉功能的影响。RNAi导致未受伤和再生的涡虫的机械感觉受损。连同机械感觉神经元中终末分化标记的丧失，这些发现确定该同源物是涡虫中机械感觉神经元特性的关键调节因子，并支持在成体组织再生过程中重新部署保守的感觉特化程序这一观点。
