The Nogo-C2/Nogo receptor complex regulates the morphogenesis of zebrafish lateral line primordium through modulating the expression of dkk1b, a Wnt signal inhibitor.
The fish lateral line (LL) is a mechanosensory system closely related to the hearing system of higher vertebrates, and it is composed of several neuromasts located on the surface of the fish. These neuromasts can detect changes in external water flow, to assist fish in maintaining a stationary position in a stream. In the present study, we identified a novel function of Nogo/Nogo receptor signaling in the formation of zebrafish neuromasts. Nogo signaling in zebrafish, like that in mammals, involves three ligands and four receptors, as well as three co-receptors (TROY, p75, and LINGO-1). We first demonstrated that Nogo-C2, NgRH1a, p75, and TROY are able to form a Nogo-C2 complex, and that disintegration of this complex causes defective neuromast formation in zebrafish. Time-lapse recording of the CldnB::lynEGFP transgenic line revealed that functional obstruction of the Nogo-C2 complex causes disordered morphogenesis, and reduces rosette formation in the posterior LL (PLL) primordium during migration. Consistent with these findings, hair-cell progenitors were lost from the PLL primordium in p75, TROY, and Nogo-C2/NgRH1a morphants. Notably, the expression levels of pea3, a downstream marker of Fgf signaling, and dkk1b, a Wnt signaling inhibitor, were both decreased in p75, TROY, and Nogo-C2/NgRH1a morphants; moreover, dkk1b mRNA injection could rescue the defects in neuromast formation resulting from knockdown of p75 or TROY. We thus suggest that a novel Nogo-C2 complex, consisting of Nogo-C2, NgRH1a, p75, and TROY, regulates Fgf signaling and dkk1b expression, thereby ensuring stable organization of the PLL primordium.
Institute of Biochemical Sciences, National Taiwan University, Taipei, Taiwan ; Institute of Biological Chemistry, Academia Sinica, Taipei, Taiwan.
Hao-Wei
HW
Han
Department of Biochemistry, Taipei Medical University, Taipei, Taiwan.
Chih-Ming
CM
Chou
Institute of Biological Chemistry, Academia Sinica, Taipei, Taiwan.
Cheng-Ying
CY
Chu
Department of Biochemistry, Taipei Medical University, Taipei, Taiwan.
Chia-Hsiung
CH
Cheng
Institute of Biological Chemistry, Academia Sinica, Taipei, Taiwan.
Chung-Hsiang
CH
Yang
Institute of Biological Chemistry, Academia Sinica, Taipei, Taiwan.
Chin-Chun
CC
Hung
Institute of Cellular and Organismic Biology, Academia Sinica, Taipei, Taiwan.
Pung-Pung
PP
Hwang
Institute of Zoology, National Taiwan University, Taipei, Taiwan.
Shyh-Jye
SJ
Lee
Institute of Cellular and Organismic Biology, Academia Sinica, Taipei, Taiwan.
Yung-Feng
YF
Liao
Institute of Biochemical Sciences, National Taiwan University, Taipei, Taiwan ; Institute of Biological Chemistry, Academia Sinica, Taipei, Taiwan.
Chang-Jen
CJ
Huang
D000818:Animals; D004625:Embryo, Nonmammalian / Q000502:physiology; D047108:Embryonic Development / Q000235:genetics; D018507:Gene Expression Regulation, Developmental / Q000235:genetics; D036341:Intercellular Signaling Peptides and Proteins / Q000235:genetics*; D053403:Lateral Line System / Q000502:physiology*; D009024:Morphogenesis / Q000235:genetics*; D009185:Myelin Proteins / Q000235:genetics*; D000070798:Nogo Proteins; D011956:Receptors, Cell Surface / Q000235:genetics*; D015398:Signal Transduction / Q000235:genetics; D060449:Wnt Signaling Pathway / Q000235:genetics*; D015027:Zebrafish; D029961:Zebrafish Proteins / Q000235:genetics*
D036341:Intercellular Signaling Peptides and Proteins; D009185:Myelin Proteins; D000070798:Nogo Proteins; C541256:Nogo receptor, zebrafish; D011956:Receptors, Cell Surface; C000592544:Rtn4a protein, zebrafish; D029961:Zebrafish Proteins; C501128:dkk1b protein, zebrafish