Hesr1和Hesr2可能作为发育中的耳蜗中Notch信号通路的早期效应分子发挥作用。

Hesr1 and Hesr2 may act as early effectors of Notch signaling in the developing cochlea.

作者信息

Hayashi Toshinori, Kokubo Hiroki, Hartman Byron H, Ray Catherine A, Reh Thomas A, Bermingham-McDonogh Olivia

机构信息

Virginia Merrill Bloedel Hearing Research Center, Department of Otolaryngology-HNS, Box 357923, USA.

出版信息

Dev Biol. 2008 Apr 1;316(1):87-99. doi: 10.1016/j.ydbio.2008.01.006. Epub 2008 Jan 18.

In cochlear development, the Notch signaling pathway is required for both the early prosensory phase and a later lateral inhibition phase. While it is known that Hes genes are important downstream mediators of Notch function in lateral inhibition, it is not known what genes function as mediators of the early prosensory function of Notch. We report that two members of the Hes-related gene family, Hesr1 and Hesr2, are expressed in the developing cochlea at a time and place that makes them excellent candidates as downstream mediators of Notch during prosensory specification. We also show that treatment of cochlear explant cultures at the time of prosensory specification with a small-molecule inhibitor of the Notch pathway mimics the results of conditional Jag1 deletion. This treatment also reduces Hesr1 and Hesr2 expression by as much as 80%. These results support the hypothesis that Hesr1 and Hesr2 are the downstream mediators of the prosensory function of Notch in early cochlear development.

在耳蜗发育过程中，Notch信号通路在早期的前感觉阶段和后期的侧向抑制阶段均发挥作用。虽然已知Hes基因是Notch功能在侧向抑制中的重要下游介质，但尚不清楚哪些基因作为Notch早期前感觉功能的介质发挥作用。我们发现，Hes相关基因家族的两个成员Hesr1和Hesr2，在发育中的耳蜗中的表达时间和位置，使其成为前感觉特化过程中Notch下游介质的理想候选者。我们还表明，在前感觉特化时，用Notch信号通路的小分子抑制剂处理耳蜗外植体培养物，其结果与条件性Jag1缺失相似。这种处理还使Hesr1和Hesr2的表达降低了多达80%。这些结果支持了以下假设：Hesr1和Hesr2是耳蜗早期发育中Notch前感觉功能的下游介质。