Check out our newest paper now online at Development! This paper describes regulation of mesoderm progenitors in the mouse tailbud. Besides members of our own lab, this research work is a collaboration with the Majewski Lab at the Genome Quebec.
In this study we demonstrate that Bmp4 maintains mesoderm progenitor gene signature in caudal mesodermal primary cultures. We found that this regulation was executed directly through factors such as Brachyury and Nkx1-2. Loss of Bmp can cause upregulation of aberrant gene signatures of heart, blood, muscle and skeletal lineages in the caudal progenitors of the tailbud. Lastly, we show that inhibition of Bmp signaling in the embryos confirm its role in expression of Brachyury as well as in preventing activation of abnormal lineages.
Abstract
Caudal somites are generated from a pool of progenitor cells located in the tailbud region. These progenitor cells form the presomitic mesoderm that gradually differentiates into somites under the action of the segmentation clock. The signals responsible for tailbud mesoderm progenitor pool maintenance during axial elongation are still elusive. Here, we show that Bmp signaling is sufficient to activate the entire mesoderm progenitor gene signature in primary cultures of caudal mesoderm cells. Bmp signaling acts through the key regulatory genes Brachyury (T) and Nkx1-2 and contributes to the activation of several other regulators of the mesoderm progenitor gene network. In the absence of Bmp signaling, tailbud mesoderm progenitor cells acquire aberrant gene expression signatures of the heart, blood, muscle and skeletal embryonic lineages. Treatment of embryos with the Bmp inhibitor Noggin confirmed the requirement for Bmp signaling for normal Brachyury expression and the prevention of abnormal lineage marker activation. Together, these results identify Bmp signaling as a non-cell autonomous signal necessary for mesoderm progenitor cell homeostasis.
Bouchard Lab @ McGill 