Role of lbx2 in the noncanonical Wnt signaling pathway for convergence and extension movements and hypaxial myogenesis in zebrafish

Lou, Q., He, J., Hu, L., and Yin, Z.
Biochimica et biophysica acta. Molecular cell research   1823(5): 1024-1032 (Journal)
Registered Authors
He, Jiangyan, Yin, Zhan
zebrafish, lbx2, noncanonical wnt, gastrulation
MeSH Terms
  • Animal Fins/cytology
  • Animal Fins/drug effects
  • Animal Fins/embryology
  • Animals
  • Body Patterning*/drug effects
  • Body Patterning*/genetics
  • Cell Movement*/drug effects
  • Cell Movement*/genetics
  • Embryo, Nonmammalian/cytology
  • Embryo, Nonmammalian/drug effects
  • Embryo, Nonmammalian/enzymology
  • Enzyme Activation/drug effects
  • Gastrulation/drug effects
  • Gastrulation/genetics
  • Gene Expression Regulation, Developmental/drug effects
  • Mesoderm/cytology
  • Mice
  • Morpholinos/pharmacology
  • Muscle Development*/genetics
  • Muscles/cytology
  • Muscles/embryology
  • RNA, Messenger/genetics
  • RNA, Messenger/metabolism
  • Repressor Proteins/genetics
  • Repressor Proteins/metabolism*
  • Stem Cells/cytology
  • Stem Cells/drug effects
  • Stem Cells/metabolism
  • Wnt Proteins/genetics
  • Wnt Proteins/metabolism
  • Wnt Signaling Pathway*/drug effects
  • Wnt Signaling Pathway*/genetics
  • Zebrafish/embryology*
  • Zebrafish/genetics
  • Zebrafish Proteins/genetics
  • Zebrafish Proteins/metabolism*
  • rhoA GTP-Binding Protein/metabolism
22406073 Full text @ BBA Molecular Cell Research

It has been suggested that mouse lbx1 is essential for directing hypaxial myogenic precursor cell migration. In zebrafish, the expression of lbx1a, lbx1b, and lbx2 has been observed in pectoral fin buds. It has also been shown that knocking down endogenous lbx2 in zebrafish embryos diminishes myoD expression in the pectoral fin bud. However, downstream lbxs signals remain largely unexplored. Here, we describe a previously unknown function of zebrafish lbx2 (lbx2) during convergent extension (CE) movements. The abrogation of the lbx2 function by two non-overlapping morpholino oligonucleotides (MOs) resulted in the defective convergence and extension movements in morphants during gastrulation. Our transplantation studies further demonstrated that the overexpression of lbx2 autonomously promotes CE movements. Expression of wnt5b is significantly reduced in lbx2 morphants. We have demonstrated that application of the wnt5b MO, a dominant-negative form of disheveled (Dvl) and a chemical inhibitor of Rho-associated kinase Y27632 in zebrafish embryos have effects reminiscent that are of the CE and hypaxial myogenesis defects observed in lbx2 morphants. Moreover, the CE and hypaxial mesoderm defects seen in lbx2 morphants can be rescued by co-injection with wnt5b or RhoA mRNA. However, this reduced level of active RhoA and hypaxial myogenesis defects in the embryos injected with the dominant-negative form of Dvl mRNA cannot be effectively restored by co-injection with lbx2 mRNA. Our results suggest that the key noncanonical Wnt signaling components Wnt5, Dvl, and RhoA are downstream effectors involved in the regulative roles of lbx2 in CE movement and hypaxial myogenesis during zebrafish embryogenesis.

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Human Disease / Model
Sequence Targeting Reagents
Engineered Foreign Genes