a vertebrate-specific chp-pak-pix pathway maintains e-cadherin at adherens junctions during zebrafish epiboly一个vertebrate-specific chp-pak-pix通路在斑马鱼外包粘合连接处并且保持钙粘蛋白.pdfVIP

A Vertebrate-Specific Chp-PAK-PIX Pathway Maintains E- Cadherin at Adherens Junctions during Zebrafish Epiboly 1 2 1,2 Hwee Goon Tay , Yuen Wai Ng , Ed Manser * 1 RGS (Rho GTPases in Stem Cells) Group, Institute of Medical Biology (IMB), Singapore, Singapore, 2 sGSK (Small G-Protein Signaling and Kinases) Group, Institute of Molecular and Cell Biology (IMCB), Neuroscience Research Partnership, Singapore, Singapore Abstract Background: In early vertebrate development, embryonic tissues modulate cell adhesiveness and acto-myosin contractility to correctly orchestrate the complex processes of gastrulation. E-cadherin (E-cadh) is the earliest expressed cadherin and is needed in the mesendodermal progenitors for efficient migration [1,2]. Regulatory mechanisms involving directed E-cadh trafficking have been invoked downstream of Wnt11/5 signaling [3]. This non-canonical Wnt pathway regulates RhoA-ROK/ DAAM1 to control the acto-myosin network. However, in this context nothing is known of the intracellular signals that participate in the correct localization of E-cadh, other than a need for Rab5c signaling [3]. Methodology/Principal Findings: By studying loss of Chp induced by morpholino-oligonucleotide injection in zebrafish, we find that the vertebrate atypical Rho-GTPase Chp is essential for the proper disposition of cells in the early embryo. The underlying defect is not leading edge F-actin assembly (prominent in the cells of the envelope layer), but rather the failure to localize E-cadh and b-catenin at the adherens junctions. Loss of Chp results in delayed epiboly that can be rescued by mRNA co-injection, and phenocopies zebrafish E-cadh mutants [4,5]. This new signaling pathway involves activation of an effector kinase PAK, and involvement of the adaptor PAK-interacti