受体氨酸激酶信号的下游分支相互依赖地作用,以塑造面部
Nicholas Hanne1, Diane Hu1, Marta Vidal-García2
1Department of Orthopaedic Surgery, University of California - San Francisco, San Francisco, California, USA.
bioRxiv : the preprint server for biology
|December 23, 2024
概括
在胚胎中抑制纤维细胞生长因子 (FGF) 受体氨酸激酶 (RTK) 下游通路破坏了面发育. 这些路径对干扰具有坚固的耐受性,这表明发展冗余.
科学领域:
- 发展生物学 发展生物学
- 分子生物学分子生物学
- 细胞生物学 细胞生物学
背景情况:
- 纤维细胞生长因子 (FGF) 信号通过神经细胞影响面发育.
- 之前的研究将前鼻过程 (FNP) 中FGF信号的增加与异形学,减少增殖和细胞定向的改变联系起来.
- 在面形态发生过程中RTK信号传递的作用表明特定的下游效应器调节细胞活动.
研究的目的:
- 研究RTK信号传导的三个下游分支 (MEK1/2,PI3K,PLCy) 在调节细胞活动中的作用.
- 确定抑制这些RTK下游途径如何影响FNP形态发生.
- 了解RTK信号在发育过程中的强度.
主要方法:
- 针对MEK1/2,PI3K和PLCy的小分子抑制剂被应用于胚 FNP.
- 抑制剂被单独和并排地使用.
- 作为对照剂,DMSO作为对照剂.
主要成果:
- 所有治疗都导致治疗的FNP侧的不对称近距离切断,未治疗侧的轻微扩张.
- 每个途径的抑制导致细胞增殖减少,并破坏了细胞导向.
- 亡水平仍然不受路径抑制的影响.
结论:
- 下游RTK信号通道对发育干扰具有强大耐受性.
- 冗余的信号系统可能有助于面发育的弹性.
- 特定的RTK效应因子对于调节FNP形态发生过程中的细胞活动至关重要.
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