Retinoic Acid Deficiency Underlies the Etiology of Midfacial Defects
Retinoic Acid Deficiency Underlies the Etiology of Midfacial Defects
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视黄酸缺乏是中面部缺陷的病因
DOI：
10.1177/00220345211062049
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发表时间：
2022
影响因子：
7.6
通讯作者：
Yamashiro T.
中科院分区：
文献类型：
--
作者：
Wu Y.;Kurosaka H.;Wang Q.;Inubushi T.;Nakatsugawa K.;Kikuchi M.;Ohara H.;Tsujimoto T.;Natsuyama S.;Shida Y.;Sandell L.L.;Trainor P.A.;Yamashiro T.
胚胎颅面发育依赖于多个面部原基的协调生长和融合，这些原基由颅神经嵴细胞填充并被面部外胚层覆盖。这些发育事件、其祖组织或信号通路的任何干扰都可能导致颅面畸形，如口面裂，这是人类最常见的出生缺陷之一。在本研究中，我们发现rdh10功能缺失导致胚胎早期发育中的额鼻过程中维甲酸（RA）信号的大量减少，从而导致各种颅面异常，包括面中裂和异位软骨结节。rdh10缺陷小鼠的面中裂与迁移后颅神经嵴细胞凋亡升高和细胞增殖紊乱以及发育中的额鼻突中alx1和alx3转录的大量减少有关。更重要的是，前脑腹侧shh信号的扩大，以及rdh10突变体通过抑制hhh信号部分消除面中缺陷，表明shh信号的错误调节是RA信号相关的面中缺陷减少的发病机制的基础。综上所述，这些数据说明了rdh10和RA信号在早期胚胎发生过程中的精确时空功能，以及它们在协调正常面中部发育所必需的分子和细胞事件中的重要性。
Embryonic craniofacial development depends on the coordinated outgrowth and fusion of multiple facial primordia, which are populated with cranial neural crest cells and covered by the facial ectoderm. Any disturbance in these developmental events, their progenitor tissues, or signaling pathways can result in craniofacial deformities such as orofacial clefts, which are among the most common birth defects in humans. In the present study, we show thatRdh10loss of function leads to a substantial reduction in retinoic acid (RA) signaling in the developing frontonasal process during early embryogenesis, which results in a variety of craniofacial anomalies, including midfacial cleft and ectopic chondrogenic nodules. Elevated apoptosis and perturbed cell proliferation in postmigratory cranial neural crest cells and a substantial reduction inAlx1andAlx3transcription in the developing frontonasal process were associated with midfacial cleft inRdh10-deficient mice. More important, expandedShhsignaling in the ventral forebrain, as well as partial abrogation of midfacial defects inRdh10mutants via inhibition ofHhsignaling, indicates that misregulation ofShhsignaling underlies the pathogenesis of reduced RA signaling-associated midfacial defects. Taken together, these data illustrate the precise spatiotemporal function ofRdh10and RA signaling during early embryogenesis and their importance in orchestrating molecular and cellular events essential for normal midfacial development.
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影响因子：
2.7
作者：
Griffin, John N.;Compagnucci, Claudia;Hu, Diane;Fish, Jennifer;Klein, Ophir;Marcucio, Ralph;Depew, Michael J.
通讯作者：
Depew, Michael J.
轴向 (HNF3β) 和视黄酸受体是斑马鱼声波刺猬启动子的调节因子
影响因子：
11.4
作者：
B. Chang;P. Blader;N. Fischer;P. Ingham;U. Strähle
通讯作者：
U. Strähle
影响因子：
2
作者：
El-Ruby, Mona;Fayez, Alaa El-Din;Abdel-Salam, Ghada M. H.
通讯作者：
Abdel-Salam, Ghada M. H.
影响因子：
3.5
作者：
Brugmann, Samantha A.;Allen, Nancy C.;Helms, Jill A.
通讯作者：
Helms, Jill A.
影响因子：
15.9
作者：
Kurosaka, Hiroshi;Iulianella, Angelo;Trainor, Paul A.
通讯作者：
Trainor, Paul A.