Bmper is required for morphogenesis of the anterior and posterior semicircular canal ducts in the developing zebrafish inner ear

Bmper is required for morphogenesis of the anterior and posterior semicircular canal ducts in the developing zebrafish inner ear
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Bmper 对于发育中的斑马鱼内耳的前半规管和后半规管的形态发生是必需的

DOI:
10.1101/2021.06.27.450014
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发表时间:
2021
期刊:
--
影响因子:
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通讯作者:
Baxendale S
Baxendale S
中科院分区:
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文献类型:
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作者:
Baxendale S

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已知BMP信号传导在脊椎动物内耳的半规管系统的发育中具有保守的功能,但其调节、靶基因和在耳形态发生期间对细胞行为的影响尚不完全清楚。我们已经表征了斑马鱼genebmper中突变的影响,该基因编码BMP信号传导的调节剂,在不同的发育背景下具有亲和抗BMP作用。b超突变胚胎的内耳发育为前半规管和后半规管的截断。为了在活胚胎中对发育中的耳朵进行成像,我们开发了一种新的转基因品系Tg(smad6b:EGFP),它在耳上皮中表现出强烈的GFP表达。形态学分析表明,在bmpermutant耳缺陷的早期阶段,半规管形成,与特定的减少BMP信号活性和特定的损失dlx5a的表达在耳背上皮。随后细胞形状的变化发生在截断部位和背外侧隔。我们所描述的这些畸形在成年后仍然存在,前、后半规管的截断持续到成年。我们的研究结果反对Bmper在规范的前基板区域,耳基板的诱导,或神经嵴的发展,在Bmper功能的过程中,以前有牵连的主要作用。相反,我们得出结论,Bmper功能在斑马鱼的一个关键要求是促进BMP信号在半规管系统的图案和形态发生。
BMP signalling is known to have a conserved function in development of the semicircular canal system of the vertebrate inner ear, but its regulation, target genes and effects on cell behaviour during otic morphogenesis are not fully understood. We have characterised the effects of mutations in the zebrafish genebmper,which codes for a regulator of BMP signalling with both pro- and anti-BMP roles in different developmental contexts. The inner ears ofbmpermutant embryos develop with truncations of the anterior and posterior semicircular canal ducts. To image the developing ear in live embryos, we have exploited a new transgenic line,Tg(smad6b:EGFP), which exhibits strong GFP expression in the otic epithelium. Morphometric analysis indicates defects in thebmpermutant ear from early stages of semicircular canal formation, correlating with a specific reduction in BMP signalling activity and specific loss ofdlx5aexpression in dorsal otic epithelium. Subsequent changes to cell shape occur at the truncation site and the dorsolateral septum. Thebmpermutations that we describe are adult viable; truncation of the anterior and posterior semicircular canal ducts persists into adulthood. Our results argue against a major role for Bmper in specification of the pre-placodal region, induction of the otic placode, or development of the neural crest, processes in which Bmper function has previously been implicated. Instead, we conclude that a key requirement for Bmper function in the zebrafish is to promote BMP signalling during patterning and morphogenesis of the semicircular canal system.
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