Cdon is essential for organ left-right patterning by regulating dorsal forerunner cells clustering and Kupffer's vesicle morphogenesis

作者全名："Deng, Zhilin; Ran, Qin; Chang, Wenqi; Li, Chengni; Li, Botong; Huang, Shuying; Huang, Jingtong; Zhang, Ke; Li, Yuanyuan; Liu, Xingdong; Liang, Yundan; Guo, Zhenhua; Huang, Sizhou"

作者地址："[Deng, Zhilin; Chang, Wenqi; Li, Chengni; Li, Botong; Huang, Shuying; Huang, Jingtong; Zhang, Ke; Huang, Sizhou] Chengdu Med Coll, Sch Basic Med Sci, Dept Anat & Histol & Embryol, Dev & Regenerat Key Lab Sichuan Prov, Chengdu, Peoples R China; [Deng, Zhilin] Luzhou Peoples Hosp, Dept Ultrasound, Luzhou, Peoples R China; [Ran, Qin] Chengdu Seventh Peoples Hosp, Dept Cardiol, Chengdu, Sichuan, Peoples R China; [Li, Yuanyuan; Liu, Xingdong; Huang, Sizhou] China Natl Nucl Corp Hosp 416, Chengdu Med Coll, Dept Neurol, Dept Cardiothorac Surg,Affiliated Hosp 2, Chengdu, Peoples R China; [Liang, Yundan] Chengdu Med Coll, Sch Basic Med Sci, Dept Pathol & Pathophysiol, Chengdu, Peoples R China; [Guo, Zhenhua] Chongqing Med Univ, Natl Clin Res Ctr Child Hlth & Disorders, Minist Educ Key Lab Child Dev & Disorders, Chongqing Key Lab Pediat,Childrens Hosp,China Int, Chongqing, Peoples R China"

通信作者："Huang, SZ (通讯作者)，Chengdu Med Coll, Sch Basic Med Sci, Dept Anat & Histol & Embryol, Dev & Regenerat Key Lab Sichuan Prov, Chengdu, Peoples R China.; Huang, SZ (通讯作者)，China Natl Nucl Corp Hosp 416, Chengdu Med Coll, Dept Neurol, Dept Cardiothorac Surg,Affiliated Hosp 2, Chengdu, Peoples R China.; Liang, YD (通讯作者)，Chengdu Med Coll, Sch Basic Med Sci, Dept Pathol & Pathophysiol, Chengdu, Peoples R China.; Guo, ZH (通讯作者)，Chongqing Med Univ, Natl Clin Res Ctr Child Hlth & Disorders, Minist Educ Key Lab Child Dev & Disorders, Chongqing Key Lab Pediat,Childrens Hosp,China Int, Chongqing, Peoples R China."

来源：FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY

ESI学科分类：MOLECULAR BIOLOGY & GENETICS

WOS号：WOS:001306610600001

JCR分区：Q1

影响因子：5.5

年份：2024

卷号：12

期号：　

开始页：　

结束页：　

文献类型：Article

关键词：cdon; left right patterning; DFCs; KV morphogenesis; cilia; nodal signaling

摘要："Cdon and boc are members of the cell adhesion molecule subfamily III Ig/fibronectin. Although they have been reported to be involved in muscle and neural development at late developmental stage, their early roles in embryonic development remain unknown. Here, we discovered that in zebrafish, cdon, but not boc, is expressed in dorsal forerunner cells (DFCs) and the epithelium of Kupffer's vesicle (KV), suggesting a potential role for cdon in organ left-right (LR) patterning. Further data showed that liver and heart LR patterning were disrupted in cdon morphants and cdon mutants. Mechanistically, we found that loss of cdon function led to defect in DFCs clustering, reduced KV lumen, and defective cilia, resulting in randomized Nodal/spaw signaling and subsequent organ LR patterning defects. Additionally, predominant distribution of a cdon morpholino (MO) in DFCs caused defects in DFC clustering, KV morphogenesis, cilia number/length, Nodal/spaw signaling, and organ LR asymmetry, similar to those observed in cdon morphants and cdon(-/-) embryos, indicating a cell-autonomous role for cdon in regulating KV formation during LR patterning. In conclusion, our data demonstrate that during gastrulation and early somitogenesis, cdon is essential for proper DFC clustering, KV formation, and normal cilia, thereby playing a critical role in establishing organ LR asymmetry."

基金机构：National Natural Science Foundation of China10.13039/501100001809

基金资助正文：We would like to thank Qiang Wang for his advice on this work; we also would like to thank the members working in our fish facility for their help in taking care of all the fish lines in this study.