Zebrafish foxc1a plays a crucial role in early somitogenesis by restricting the expression of aldh1a2 directly.
Foxc1a is a member of the forkhead transcription factors. It plays an essential role in zebrafish somitogenesis. However, little is known about the molecular mechanisms underlying its controlling somitogenesis. To uncover how foxc1a regulates zebrafish somitogenesis, we generated foxc1a knock-out zebrafish using TALEN (transcription activator-like effector nuclease) technology. The foxc1a null embryos exhibited defective somites at early development. Analyses on the expressions of the key genes that control processes of somitogenesis revealed that foxc1a controlled early somitogenesis by regulating the expression of myod1. In the somites of foxc1a knock-out embryos, expressions of fgf8a and deltaC were abolished, whereas the expression of aldh1a2 (responsible for providing retinoic acid signaling) was significantly increased. Once the increased retinoic acid level in the foxc1a null embryos was reduced by knocking down aldh1a2, the reduced expression of myod1 was partially rescued by resuming expressions of fgf8a and deltaC in the somites of the mutant embryos. Moreover, a chromatin immunoprecipitation assay on zebrafish embryos revealed that Foxc1a bound aldh1a2 promoter directly. On the other hand, neither knocking down fgf8a nor inhibiting Notch signaling affected the expression of aldh1a2, although knocking down fgf8a reduced expression of deltaC in the somites of zebrafish embryos at early somitogenesis and vice versa. Taken together, our results demonstrate that foxc1a plays an essential role in early somitogenesis by controlling Fgf and Notch signaling through restricting the expression of aldh1a2 in paraxial mesoderm directly.
From the MOE Key Laboratory of Model Animal for Disease Study, Model Animal Research Center, Nanjing University, Nanjing 210061, China and the Maternal and Child Health Medical Institute, Nanjing Maternal and Child Health Care Hospital Affiliated with Nanjing Medical University, Nanjing 210004, China.
Jingyun
J
Li
From the MOE Key Laboratory of Model Animal for Disease Study, Model Animal Research Center, Nanjing University, Nanjing 210061, China and.
Yunyun
Y
Yue
From the MOE Key Laboratory of Model Animal for Disease Study, Model Animal Research Center, Nanjing University, Nanjing 210061, China and.
Xiaohua
X
Dong
From the MOE Key Laboratory of Model Animal for Disease Study, Model Animal Research Center, Nanjing University, Nanjing 210061, China and.
Wenshuang
W
Jia
From the MOE Key Laboratory of Model Animal for Disease Study, Model Animal Research Center, Nanjing University, Nanjing 210061, China and.
Kui
K
Li
From the MOE Key Laboratory of Model Animal for Disease Study, Model Animal Research Center, Nanjing University, Nanjing 210061, China and.
Dong
D
Liang
From the MOE Key Laboratory of Model Animal for Disease Study, Model Animal Research Center, Nanjing University, Nanjing 210061, China and.
Zhangji
Z
Dong
From the MOE Key Laboratory of Model Animal for Disease Study, Model Animal Research Center, Nanjing University, Nanjing 210061, China and.
Xiaoxiao
X
Wang
From the MOE Key Laboratory of Model Animal for Disease Study, Model Animal Research Center, Nanjing University, Nanjing 210061, China and.
Xiaoxi
X
Nan
From the MOE Key Laboratory of Model Animal for Disease Study, Model Animal Research Center, Nanjing University, Nanjing 210061, China and.
Qinxin
Q
Zhang
From the MOE Key Laboratory of Model Animal for Disease Study, Model Animal Research Center, Nanjing University, Nanjing 210061, China and qingshun@nju.edu.cn.
Qingshun
Q
Zhao
D000818:Animals; D030801:Animals, Genetically Modified; D019521:Body Patterning / Q000235:genetics*; D004625:Embryo, Nonmammalian; D005346:Fibroblast Growth Factors / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D051858:Forkhead Transcription Factors / Q000235:genetics* / Q000378:metabolism; D018507:Gene Expression Regulation, Developmental; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics / Q000378:metabolism; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism; D017570:MyoD Protein / Q000235:genetics / Q000378:metabolism; D011401:Promoter Regions, Genetic; D051880:Receptors, Notch / Q000235:genetics / Q000378:metabolism; D050697:Retinal Dehydrogenase / Q000235:genetics* / Q000378:metabolism; D015398:Signal Transduction; D019170:Somites / Q000254:growth & development / Q000378:metabolism*; D014212:Tretinoin / Q000378:metabolism; D015027:Zebrafish / Q000235:genetics* / Q000254:growth & development / Q000378:metabolism; D029961:Zebrafish Proteins / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000378:metabolism
D051858:Forkhead Transcription Factors; C426857:Foxc1a protein, zebrafish; D047908:Intracellular Signaling Peptides and Proteins; D008565:Membrane Proteins; D017570:MyoD Protein; C057363:MyoD1 myogenic differentiation protein; D051880:Receptors, Notch; D029961:Zebrafish Proteins; C064045:delta protein; C517774:fgf8a protein, zebrafish; D014212:Tretinoin; D005346:Fibroblast Growth Factors; C518907:Aldh1a2 protein, zebrafish; D050697:Retinal Dehydrogenase
Fibroblast Growth Factor (FGF); MyoD; Paraxial Mesoderm; Retinoic Acid; Somitogenesis; Transcription Activator-like Effector Nuclease (TALEN); Zebrafish; aldh1a2; deltaC; foxc1a