title: β-Catenin 1 and β-catenin 2 play similar and distinct roles in left-right asymmetric development of zebrafish embryos.
abstract: β-Catenin-mediated canonical Wnt signaling has been found to be required for left-right (LR) asymmetric development. However, the implication of endogenous β-catenin in LR development has not been demonstrated by loss-of-function studies. In zebrafish embryos, two β-catenin genes, β-catenin 1 (ctnnb1) and β-catenin 2 (ctnnb2) are maternally expressed and their zygotic expression occurs in almost all types of tissues, including Kupffer's vesicle (KV), an essential organ that initiates LR development in teleost fish. We demonstrate here that morpholino-mediated knockdown of ctnnb1, ctnnb2, or both, in the whole embryo or specifically in dorsal forerunner cells (DFCs) interrupts normal asymmetry of the heart, liver and pancreas. Global knockdown of ctnnb2 destroys the midline physical and molecular barrier, while global knockdown of ctnnb1 impairs the formation of the midline molecular barrier. Depletion of either gene or both in DFCs/KV leads to poor KV cell proliferation, abnormal cilia formation and disordered KV fluid flow with downregulation of ntl and tbx16 expression. ctnnb1 and ctnnb2 in DFCs/KV differentially regulate the expression of charon, a Nodal antagonist, and spaw, a key Nodal gene for laterality development in zebrafish. Loss of ctnnb1 in DFCs/KV inhibits the expression of charon around KV and of spaw in the posterior lateral plate mesoderm, while ctnnb2 knockdown results in loss of spaw expression in the anterior lateral plate mesoderm with little alteration of charon expression. Taken together, our findings suggest that ctnnb1 and ctnnb2 regulate multiple processes of laterality development in zebrafish embryos through similar and distinct mechanisms.
authors.affiliation: State Key Laboratory of Biomembrane and Membrane Engineering, Tsinghua-Peking Center for Life Sciences, School of Life Sciences, Tsinghua University, Beijing 100084, China.
authors.forename: Min
authors.initials: M
authors.lastname: Zhang
authors.forename: Junfeng
authors.initials: J
authors.lastname: Zhang
authors.forename: Sheng-Cai
authors.initials: SC
authors.lastname: Lin
authors.forename: Anming
authors.initials: A
authors.lastname: Meng
mesh_terms: D000818:Animals; D019521:Body Patterning / Q000502:physiology*; D049109:Cell Proliferation; D005326:Fetal Proteins; D018507:Gene Expression Regulation, Developmental / Q000235:genetics / Q000502:physiology*; D055785:Gene Knockdown Techniques; D007091:Image Processing, Computer-Assisted; D017403:In Situ Hybridization; D018613:Microscopy, Confocal; D008863:Microspheres; D060172:Morpholinos; D020825:T-Box Domain Proteins / Q000378:metabolism; D060449:Wnt Signaling Pathway / Q000502:physiology*; D015027:Zebrafish / Q000196:embryology*; D029961:Zebrafish Proteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D051176:beta Catenin / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D000098908:Brachyury Protein
chemical_list: D005326:Fetal Proteins; D060172:Morpholinos; D020825:T-Box Domain Proteins; D029961:Zebrafish Proteins; D051176:beta Catenin; D000098908:Brachyury Protein; C495269:ctnnb1 protein, zebrafish; C486227:dand5 protein, zebrafish; C112539:tbx16 protein, zebrafish