The Fuzzy planar cell polarity protein (FUZ), necessary for primary cilium formation, is essential for pituitary development.
The Fuzzy planar cell polarity protein (FUZ), necessary for primary cilium formation, is essential for pituitary development.
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DOI：
10.1111/joa.13961
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发表时间：
2024-02
影响因子：
2.4
通讯作者：
Andoniadou, Cynthia L.
中科院分区：
文献类型：
--
作者：
Lodge, Emily J.;Barrell, William B.;Liu, Karen J.;Andoniadou, Cynthia L.
初级纤毛是一种重要的细胞器，在发育和稳态过程中对正常细胞信号传导非常重要，但其在垂体发育中的作用尚未报道。初级纤毛促进多个途径的信号转导，最具特征的是SHH途径，已知这是正确的垂体发育所必需的。FUZ是一种平面细胞极性（PCP）效应子，对正常纤毛发生至关重要，其中Fuz −/−突变体的初级纤毛较短或无功能。FUZ是招募逆行鞭毛内转运蛋白到细胞器基部所需的一组蛋白质的一部分。先前的工作已经报道了Fuz −/−纯合无效小鼠突变体的纤毛病变表型，包括神经管缺陷，颅面畸形和多指（趾）畸形，以及PCP缺陷，包括扭结/卷曲尾巴和心脏缺陷。有趣的是，据报道Fuz −/−突变体在14.5 dpc时缺失脑垂体，但未研究这种表型的机制。在这里，我们分析了Fuz −/−突变体的垂体发育。组织学分析表明，Rathke囊（RP）最初是正常诱导的，但没有指定，不能表达LHX 3，导致发育不良和凋亡。SHH信号的表征揭示了Fuz −/−突变体相对于对照胚胎的通路激活减少，导致垂体前叶命运的缺乏规范。对受SHH影响的关键发育信号FGF 8和BMP 4的分析揭示了腹侧间脑的异常模式，进一步促进了RP的异常发育。两者合计，我们的分析表明，初级纤毛需要通过SHH信号正常垂体规格。这份手稿表明，初级纤毛是一个重要的细胞器为垂体腺的发展和内分泌紊乱的垂体腺可以表现为纤毛。
The primary cilium is an essential organelle that is important for normal cell signalling during development and homeostasis but its role in pituitary development has not been reported. The primary cilium facilitates signal transduction for multiple pathways, the best‐characterised being the SHH pathway, which is known to be necessary for correct pituitary gland development. FUZ is a planar cell polarity (PCP) effector that is essential for normal ciliogenesis, where the primary cilia of Fuz −/− mutants are shorter or non‐functional. FUZ is part of a group of proteins required for recruiting retrograde intraflagellar transport proteins to the base of the organelle. Previous work has reported ciliopathy phenotypes in Fuz −/− homozygous null mouse mutants, including neural tube defects, craniofacial abnormalities, and polydactyly, alongside PCP defects including kinked/curly tails and heart defects. Interestingly, the pituitary gland was reported to be missing in Fuz −/− mutants at 14.5 dpc but the mechanisms underlying this phenotype were not investigated. Here, we have analysed the pituitary development of Fuz −/− mutants. Histological analyses reveal that Rathke's pouch (RP) is initially induced normally but is not specified and fails to express LHX3, resulting in hypoplasia and apoptosis. Characterisation of SHH signalling reveals reduced pathway activation in Fuz −/− mutant relative to control embryos, leading to deficient specification of anterior pituitary fate. Analyses of the key developmental signals FGF8 and BMP4, which are influenced by SHH, reveal abnormal patterning in the ventral diencephalon, contributing further to abnormal RP development. Taken together, our analyses suggest that primary cilia are required for normal pituitary specification through SHH signalling. This manuscript shows that the primary cilium is an essential organelle for pituitary gland development and that endocrine disturbance of the pituitary gland can be a manifestation of ciliopathies.
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DOI：
10.3390/children10040647
发表时间：
2023-03-30
期刊：
Children (Basel, Switzerland)
影响因子：
--
作者：
通讯作者：
--
DOI：
10.1002/ajmg.1320070111
发表时间：
1980-01-01
期刊：
AMERICAN JOURNAL OF MEDICAL GENETICS
影响因子：
--
作者：
CLARREN, SK;ALVORD, EC;HALL, JG
通讯作者：
HALL, JG
DOI：
10.1002/ajmg.1320070110
发表时间：
1980-01-01
期刊：
AMERICAN JOURNAL OF MEDICAL GENETICS
影响因子：
--
作者：
HALL, JG;PALLISTER, PD;REED, SD
通讯作者：
REED, SD
影响因子：
3.5
作者：
Böse, J;Grotewold, L;Rüther, U
通讯作者：
Rüther, U
影响因子：
11.8
作者：
Zhao, Li;Zevallos, Solsire E.;Rizzoti, Karine;Jeong, Yongsu;Lovell-Badge, Robin;Epstein, Douglas J.
通讯作者：
Epstein, Douglas J.