Esrrγa regulates nephron and ciliary development by controlling prostaglandin synthesis.
Esrrγa regulates nephron and ciliary development by controlling prostaglandin synthesis.
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DOI：
10.1242/dev.201411
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发表时间：
2023-05-15
期刊：
影响因子：
4.6
通讯作者：
Wingert, Rebecca A.
中科院分区：
文献类型：
--
作者：
Wesselman, Hannah M.;Flores-Mireles, Ana L.;Bauer, Aidan;Pei, Liming;Wingert, Rebecca A.
纤毛对于包括肾脏在内的许多组织的个体发育和功能至关重要。在此，我们报道转录因子 ERRγ 直系同源雌激素相关受体 γa (Esrrγa) 对于斑马鱼肾细胞命运选择和纤毛发生至关重要。 esrrγa 缺陷改变了近远端肾单位模式，减少了多纤毛细胞群，并扰乱了肾单位、库普弗囊泡和耳囊的纤毛发生。这些表型与前列腺素信号传导的中断一致，我们发现纤毛发生被 PGE2 或环氧合酶 Ptgs1 拯救。遗传相互作用表明，过氧化物酶体增殖物激活受体 γ、辅激活子 1 α (Ppargc1a) 在 Ptgs1 介导的前列腺素合成上游发挥作用，与纤毛途径中的 Esrrγa 具有协同关系。这些纤毛病表型也在缺乏肾上皮细胞（REC）ERRγ的小鼠中观察到，其中近端和远端肾小管细胞上形成的纤毛明显较短。在 REC-ERRγ 敲除小鼠中，纤毛长度缩短先于囊肿形成，这表明纤毛变化在发病过程的早期发生。这些数据通过调节前列腺素信号传导并与 Ppargc1a 合作，将 Esrrγa 定位为纤毛发生和肾发生之间的新联系。摘要：孤儿核受体 Esrrγa 调节斑马鱼和小鼠肾脏器官发生和纤毛发育的发现促进了对纤毛病的理解。
Cilia are essential for the ontogeny and function of many tissues, including the kidney. Here, we report that transcription factor ERRγ ortholog estrogen related receptor gamma a (Esrrγa) is essential for renal cell fate choice and ciliogenesis in zebrafish. esrrγa deficiency altered proximodistal nephron patterning, decreased the multiciliated cell populace and disrupted ciliogenesis in the nephron, Kupffer's vesicle and otic vesicle. These phenotypes were consistent with interruptions in prostaglandin signaling, and we found that ciliogenesis was rescued by PGE2 or the cyclooxygenase enzyme Ptgs1. Genetic interaction revealed that peroxisome proliferator-activated receptor gamma, coactivator 1 alpha (Ppargc1a), which acts upstream of Ptgs1-mediated prostaglandin synthesis, has a synergistic relationship with Esrrγa in the ciliogenic pathway. These ciliopathic phenotypes were also observed in mice lacking renal epithelial cell (REC) ERRγ, where significantly shorter cilia formed on proximal and distal tubule cells. Decreased cilia length preceded cyst formation in REC-ERRγ knockout mice, suggesting that ciliary changes occur early during pathogenesis. These data position Esrrγa as a novel link between ciliogenesis and nephrogenesis through regulation of prostaglandin signaling and cooperation with Ppargc1a. Summary: Understanding of ciliopathy disorders has been advanced by the discovery that the orphan nuclear receptor Esrrγa regulates kidney organogenesis and ciliary development in zebrafish and the mouse.
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影响因子：
4.5
作者：
Bertrand S;Thisse B;Tavares R;Sachs L;Chaumot A;Bardet PL;Escrivà H;Duffraisse M;Marchand O;Safi R;Thisse C;Laudet V
通讯作者：
Laudet V
影响因子：
5.5
作者：
Tingler, Melanie;Brugger, Amelie;Feistel, Kerstin;Schweickert, Axel
通讯作者：
Schweickert, Axel
影响因子：
4.6
作者：
Chambers, Brooke E.;Gerlach, Gary F.;Wingert, Rebecca A.
通讯作者：
Wingert, Rebecca A.
影响因子：
1.2
作者：
Cheng, Christina N.;Li, Yue;Wingert, Rebecca A.
通讯作者：
Wingert, Rebecca A.
影响因子：
3.1
作者：
Chambers JM;Wingert RA
通讯作者：
Wingert RA