دورية
The embryonic patterning gene Dbx1governs the survival of the auditory midbrain via Tcf7l2-Ap2δtranscriptional cascade
العنوان: | The embryonic patterning gene Dbx1governs the survival of the auditory midbrain via Tcf7l2-Ap2δtranscriptional cascade |
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المؤلفون: | Tran, Hong-Nhung, Nguyen, Quy-Hoai, Jeong, Ji-eun, Loi, Duc-Linh, Nam, Youn Hee, Kang, Tong Ho, Yoon, Jaeseung, Baek, Kwanghee, Jeong, Yongsu |
المصدر: | Cell Death and Differentiation; 20230101, Issue: Preprints p1-12, 12p |
مستخلص: | At the top of the midbrain is the inferior colliculus (IC), which functions as the major hub for processing auditory information. Despite the functional significance of neurons in the IC, our understanding of their formation is limited. In this study, we identify the embryonic patterning gene Dbx1as a key molecular player that governs genetic programs for IC survival. We find that Dbx1plays a critical role in preventing apoptotic cell death in postnatal IC by transcriptionally repressing c-Junand pro-apoptotic BH3 only factors. Furthermore, by employing combined approaches, we uncover that Tcf7l2functions downstream of Dbx1. Loss of Tcf7l2function causes IC phenotypes with striking similarity to those of Dbx1mutant mice, which include defective embryonic maturation and postnatal deletion of the IC. Finally, we demonstrate that the Dbx1-Tcf7l2cascade functions upstream of Ap-2δ, which is essential for IC development and survival. Together, these results unravel a novel molecular mechanism for IC maintenance, which is indispensable for normal brain development. |
قاعدة البيانات: | Supplemental Index |
تدمد: | 13509047 14765403 |
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DOI: | 10.1038/s41418-023-01165-6 |