Smad1 transcription factor integrates BMP2 and Wnt3a signals in migrating cardiac progenitor cells

Song, Junfang, Mccoll, James, Camp Navarro, Ester, Kennerley, Nicola, Mok, Geoffrey, Mccormick, Dominique, Grocott, Timothy, Wheeler, Grant and Munsterberg, Andrea (2014) Smad1 transcription factor integrates BMP2 and Wnt3a signals in migrating cardiac progenitor cells. Proceedings of the National Academy of Sciences, 111 (20). pp. 7337-7342. ISSN 0027-8424

[img]
Preview
PDF (PNAS-2014-Song-7337-42) - Published Version
Download (1MB) | Preview

Abstract

In vertebrate embryos, cardiac progenitor cells (CPCs) undergo long-range migration after emerging from the primitive streak during gastrulation. Together with other mesoderm progenitors, they migrate laterally and then toward the ventral midline, where they form the heart. Signals controlling the migration of different progenitor cell populations during gastrulation are poorly understood. Several pathways are involved in the epithelial-to-mesenchymal transition and ingression of mesoderm cells through the primitive streak, including fibroblast growth factors and wingless-type family members (Wnt). Here we focus on early CPC migration and use live video microscopy in chicken embryos to demonstrate a role for bone morphogenetic protein (BMP)/SMA and MAD related (Smad) signaling. We identify an interaction of BMP and Wnt/glycogen synthase kinase 3 beta (GSK3β) pathways via the differential phosphorylation of Smad1. Increased BMP2 activity altered migration trajectories of prospective cardiac cells and resulted in their lateral displacement and ectopic differentiation, as they failed to reach the ventral midline. Constitutively active BMP receptors or constitutively active Smad1 mimicked this phenotype, suggesting a cell autonomous response. Expression of GSK3β, which promotes the turnover of active Smad1, rescued the BMP-induced migration phenotype. Conversely, expression of GSK3β-resistant Smad1 resulted in aberrant CPC migration trajectories. De-repression of GSK3β by dominant negative Wnt3a restored normal migration patterns in the presence of high BMP activity. The data indicate the convergence of BMP and Wnt pathways on Smad1 during the early migration of prospective cardiac cells. Overall, we reveal molecular mechanisms that contribute to the emerging paradigm of signaling pathway integration in embryo development.

Item Type: Article
Uncontrolled Keywords: live imaging,cell tracking,q science ,/dk/atira/pure/core/keywords/q
Faculty \ School: Faculty of Science > School of Biological Sciences
Depositing User: Pure Connector
Date Deposited: 23 Jun 2016 23:02
Last Modified: 24 Jun 2020 23:49
URI: https://ueaeprints.uea.ac.uk/id/eprint/59487
DOI: 10.1073/pnas.1321764111

Actions (login required)

View Item View Item