Wnt3a-mediated chemorepulsion controls movement patterns of cardiac progenitors and requires RhoA function

Qiaoyun Yue, Laura Wagstaff, Xuesong Yang, Cornelis Weijer, Andrea Munsterberg

    Research output: Contribution to journalArticle

    61 Citations (Scopus)

    Abstract

    The heart is the first organ to function during vertebrate development and cardiac progenitors are among the first cell lineages to be established. In the chick, cardiac progenitors have been mapped in the epiblast of pre-streak embryos, and in the early gastrula they are located in the mid-primitive streak, from which they enter the mesoderm bilaterally. Signals controlling the specification of cardiac cells have been well documented; however, migration routes of cardiac progenitors have not been directly observed within the embryo and the factor(s) controlling their movement are not known. In addition, it is not clear how cell movement is coordinated with cell specification in the early embryo. Here we use live imaging to show that cardiac progenitors migrate in highly directed trajectories, which can be controlled by Wnt3a. Ectopic Wnt3a altered movement trajectories and caused cardia bifida. This was rescued by electroporation of dominant-negative DN-Wnt3a into prospective cardiac cells. Explant essays and mutant analysis showed that cellular guidance involved repulsion in response to Wnt3a and required RhoA function. It has been shown that Wnt3a inhibits cardiogenic cell specification through a beta-catenin-dependent pathway. On the basis of our results, we propose that Wnt3a concomitantly guides the movement of cardiac progenitors by a novel mechanism involving RhoA-dependent chemorepulsion.

    Original languageEnglish
    Pages (from-to)1029-1037
    Number of pages9
    JournalDevelopment
    Volume135
    Issue number6
    DOIs
    Publication statusPublished - 15 Mar 2008

    Keywords

    • Wnt signalling
    • Cell migration
    • Chemorepulsion
    • Cardiac progenitors
    • Chick
    • Primitive streak form
    • Beta catenin
    • Chick embryo
    • Heart development
    • Gene expression
    • Cell movement
    • Family members
    • WNT
    • Mesoderm
    • Gastrulation

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