Inactivation of Fgf3 and Fgf4 within the Fgf3/Fgf4/Fgf15 gene cluster reveals their redundant requirement for mouse inner ear induction and embryonic survival.

Inactivation of Fgf3 and Fgf4 within the Fgf3/Fgf4/Fgf15 gene cluster reveals their redundant requirement for mouse inner ear induction and embryonic survival.
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DOI:
10.1002/dvdy.435
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发表时间:
2022-05
期刊:
Developmental dynamics : an official publication of the American Association of Anatomists
影响因子:
--
通讯作者:
--
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其他
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成纤维细胞生长因子(Fgfs)是胚胎发生过程中存活和器官形成所必需的。Fgfs经常冗余地执行它们的功能。先前的分析显示Fgf3突变体对内耳形成和胚胎存活的影响具有不完全外显性。在这里,我们发现一个新霉素耐药基因(neo)取代Fgf3编码区导致胚胎发育期间存活率降低和内耳缺陷的外显率增加。Fgf3neo/neo突变体显示Fgf4的表达降低,Fgf4位于小鼠基因组中靠近Fgf3位点的位置。在Fgf3缺失的背景下,使用Fgf3/4顺式小鼠进行内耳发育过程中Fgf4的条件失活,揭示了在耳位诱导过程中这些Fgfs之间的冗余需求。相比之下,Fgf3和Fgf4在咽部的失活并不会影响咽部弓的发展,在咽部,这两种Fgf3和Fgf4也使用Foxg1-Cre驱动因子共同表达。然而,这些突变体的围产期存活率降低。这些结果强调了Fgf信号在发育过程中的重要性。特别是,Fgf家族的不同成员冗余地保证内耳形成和胚胎存活。
Fibroblast growth factors (Fgfs) are required for survival and organ formation during embryogenesis. Fgfs often execute their functions redundantly. Previous analysis of Fgf3 mutants revealed effects on inner ear formation and embryonic survival with incomplete penetrance. Here, we show that presence of a neomycin resistance gene (neo) replacing the Fgf3 coding region leads to reduced survival during embryogenesis and an increased penetrance of inner ear defects. Fgf3neo/neo mutants showed reduced expression of Fgf4, which is positioned in close proximity to the Fgf3 locus in the mouse genome. Conditional inactivation of Fgf4 during inner ear development on a Fgf3 null background using Fgf3/4 cis mice revealed a redundant requirement between these Fgfs during otic placode induction. In contrast, inactivation of Fgf3 and Fgf4 in the pharyngeal region where both Fgfs are also co-expressed using a Foxg1-Cre driver did not affect development of the pharyngeal arches. However, these mutants showed reduced perinatal survival. These results highlight the importance of Fgf signaling during development. In particular, different members of the Fgf family act redundantly to guarantee inner ear formation and embryonic survival.
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