Upregulation of GBP1 in thyroid primordium is required for developmental thyroid morphogenesis.
Upregulation of GBP1 in thyroid primordium is required for developmental thyroid morphogenesis.
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甲状腺原基中 GBP1 的上调是甲状腺发育形态发生所必需的
DOI：
10.1038/s41436-021-01237-3
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发表时间：
2021-10
期刊：
影响因子：
--
通讯作者：
Song HD
中科院分区：
文献类型：
--
作者：
Yang RM;Zhan M;Zhou QY;Ye XP;Wu FY;Dong M;Sun F;Fang Y;Zhang RJ;Zhang CR;Yang L;Guo MM;Zhang JX;Liang J;Cheng F;Liu W;Han B;Zhou Y;Zhao SX;Song HD
目的：第二生殖器甲状腺功能减退症（CH）是人类常见的先天性内分泌疾病。ch相关疾病，如甲状腺萎缩、甲状腺异位和发育不全，主要是由甲状腺发育不良引起的。然而，潜在的分子机制仍然未知。方法为了鉴定新的CH候选基因，纳入192例CH患者，对21个已知CH相关基因进行靶测序。其余98例未携带已知基因的CH患者进行外显子组测序（ES）。在体外甲状腺上皮细胞和斑马鱼模型生物中证实了所鉴定的变异的功能。结果从3例患者中鉴定出4种gbp1致病变异。在斑马鱼胚胎中，gbp1敲低导致甲状腺原基形态发生缺陷和甲状腺功能减退。在缺乏bp1的胚胎中，甲状腺细胞粘在一起，无法相互分离形成单独的卵泡。此外，除了突变的hGBP1（p. 1）外，其他缺陷都用野生型humanGBP1（hGBP1）信使RNA （mRNA）修复。H150Y, p.L187P)过表达。GBP1促进β-连环蛋白转运到细胞质中，抑制细胞粘附复合物的形成。抑制细胞-细胞粘附可恢复bp1缺陷斑马鱼胚胎甲状腺原基生长缺陷。结论本研究为甲状腺发育提供了进一步的认识，表明细胞重塑缺陷可能导致先天性甲状腺功能减退。
PurposeCongenital hypothyroidism (CH) is a common congenital endocrine disorder in humans. CH-related diseases such as athyreosis, thyroid ectopy, and hypoplasia are primarily caused by dysgenic thyroid development. However, the underlying molecular mechanisms remain unknown.MethodsTo identify novel CH candidate genes, 192 CH patients were enrolled, and target sequencing of 21 known CH-related genes was performed. The remaining 98 CH patients carrying no known genes were subjected to exome sequencing (ES). The functions of the identified variants were confirmed using thyroid epithelial cells in vitro and in zebrafish model organisms in vivo.ResultsFour pathogenicGBP1variations from three patients were identified. In zebrafish embryos,gbp1knockdown caused defective thyroid primordium morphogenesis and hypothyroidism. The thyroid cells were stuck together and failed to dissociate from each other to form individual follicles ingbp1-deficient embryos. Furthermore, defects were restored with wild-type humanGBP1(hGBP1) messenger RNA (mRNA) except for mutatedhGBP1(p.H150Y, p.L187P) overexpression. GBP1 promoted β-catenin translocation into the cytosol and suppressed the formation of cellular adhesion complexes. Suppression of cell–cell adhesion restored the thyroid primordium growth defect observed ingbp1-deficient zebrafish embryos.ConclusionThis study provides further understanding regarding thyroid development and shows that defective cellular remodeling could cause congenital hypothyroidism.
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影响因子：
3.8
作者：
Quintero M;Adamoski D;Reis LMD;Ascenção CFR;Oliveira KRS;Gonçalves KA;Dias MM;Carazzolle MF;Dias SMG
通讯作者：
Dias SMG
影响因子：
--
作者：
Pannekoek, Willem-Jan;de Rooij, Johan;Gloerich, Martijn
通讯作者：
Gloerich, Martijn
影响因子：
2.4
作者：
Loebel DA;Plageman TF Jr;Tang TL;Jones VJ;Muccioli M;Tam PP
通讯作者：
Tam PP
影响因子：
2.9
作者：
Daumke, Oliver;Praefcke, Gerrit J. K.
通讯作者：
Praefcke, Gerrit J. K.
影响因子：
2.5
作者：
KIMMEL, CB;BALLARD, WW;SCHILLING, TF
通讯作者：
SCHILLING, TF