Divergent requirements for fibroblast growth factor signaling in zebrafish maxillary barbel and caudal fin regeneration.

Divergent requirements for fibroblast growth factor signaling in zebrafish maxillary barbel and caudal fin regeneration.
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DOI:
10.1111/dgd.12035
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发表时间:
2013-02
期刊:
Development, growth & differentiation
影响因子:
--
通讯作者:
LeClair EE
LeClair EE
中科院分区:
其他
文献类型:
--
作者:
Duszynski RJ;Topczewski J;LeClair EE

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斑马鱼上颌倒钩是一个由皮肤、腺体、色素细胞、味蕾、神经和内皮血管组成的表皮器官。上颌须能再生;然而,对其分子调控机制知之甚少。我们研究了鱼刺再生过程中FGF相关的信号分子,并将其与众所周知的再生附属物斑马鱼尾鳍进行了比较。多个FGF配体(fgf20a, fgf24),受体(fgfr1-4)和下游靶标(pea3, il17d)在正常和再生的鱼刺组织中表达,证实了FGF的激活。为了测试刺须再生是否需要特定的FGF通路,我们在两个温度依赖性的斑马鱼系中同时进行了刺须和尾鳍截肢。尾鳍囊胚形成的关键因子fgf20a点突变纯合的斑马鱼可以正常再生上颌刺,这表明对这种配体的需求是附属物特异性的。FGF阴性受体Tg(hsp701:dn-fgfr1:EGFP)pd1在全球范围内的过表达完全阻断了鳍的生长,但仅部分抑制了倒刺的生长,表明倒刺组织对FGF的需求降低。表达dn-fgfr1的上颌倒钩再生周围神经、真皮结缔组织、内皮管和腺上皮;与最近报道的dn-fgfr1过表达阻断斑马鱼幼虫咽味蕾形成相反,我们观察到calretinin阳性味蕾的强大形成。这是首次探索上颌倒刺再生分子机制的实验。我们的研究结果表明,在不同的斑马鱼附属物(尾鳍与上颌倒刺)和不同胚胎来源的味蕾(咽内胚层与倒刺外胚层)的再生过程中,FGF信号的需求是不同的。
The zebrafish maxillary barbel is an integumentary organ containing skin, glands, pigment cells, taste buds, nerves, and endothelial vessels. The maxillary barbel can regenerate; however, little is know about its molecular regulation. We have studied FGF-related signaling molecules during barbel regeneration, comparing these to a well-known regenerating appendage, the zebrafish caudal fin. Multiple FGF ligands (fgf20a, fgf24), receptors (fgfr1–4) and downstream targets (pea3, il17d) are expressed in normal and regenerating barbel tissue, confirming FGF activation. To test if specific FGF pathways were required for barbel regeneration, we performed simultaneous barbel and caudal fin amputations in two temperature-dependent zebrafish lines. Zebrafish homozygous for a point mutation in fgf20a, a factor essential for caudal fin blastema formation, regrew maxillary barbels normally, indicating that the requirement for this ligand is appendage-specific. Global overexpression of a dominant negative FGF receptor, Tg(hsp70l:dn-fgfr1:EGFP)pd1 completely blocked fin outgrowth but only partially inhibited barbel outgrowth, suggesting reduced requirements for FGFs in barbel tissue. Maxillary barbels expressing dn-fgfr1 regenerated peripheral nerves, dermal connective tissue, endothelial tubes, and a glandular epithelium; in contrast to a recent report in which dn-fgfr1 overexpression blocks pharyngeal taste bud formation in zebrafish larvae, we observed robust formation of calretinin-positive tastebuds. These are the first experiments to explore the molecular mechanisms of maxillary barbel regeneration. Our results suggest heterogeneous requirements for FGF signaling in the regeneration of different zebrafish appendages (caudal fin vs. maxillary barbel) and taste buds of different embryonic origin (pharyngeal endoderm vs. barbel ectoderm).
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