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  • Tissue specific requirements for WNT11 in developing outflow tract and dorsal mesenchymal protrusion.

Tissue specific requirements for WNT11 in developing outflow tract and dorsal mesenchymal protrusion.

Developmental biology (2017-07-04)
Patrick P van Vliet, Lizhu Lin, Cornelis J Boogerd, James F Martin, Gregor Andelfinger, Paul D Grossfeld, Sylvia M Evans
ABSTRACT

Correct cardiac development is essential for fetal and adult life. Disruptions in a variety of signaling pathways result in congenital heart defects, including outflow and inflow tract defects. We previously found that WNT11 regulates outflow tract development. However, tissue specific requirements for WNT11 in this process remain unknown and whether WNT11 is required for inflow tract development has not been addressed. Here we find that germline Wnt11 null mice also show hypoplasia of the dorsal mesenchymal protrusion (DMP), which is required for atrioventricular septation. Ablation of Wnt11 with myocardial cTnTCre recapitulated outflow tract defects observed in germline Wnt11 null mice, but DMP development was unaffected. In contrast, ablation of Wnt11 with Isl1Cre fully recapitulated both outflow tract and DMP defects of Wnt11 germline nulls. DMP hypoplasia in Wnt11 mutants was associated with reduced proliferation within the DMP, but no evident defects in myocardial differentiation of the DMP. Examination of Pitx2-, Axin2-, or Patched-lacZ reporter mice revealed no alterations in reporter expression, suggesting that WNT11 was required downstream of, or in parallel to, these signaling pathways to regulate DMP formation. These studies revealed a previously unappreciated role for WNT11 for DMP formation and distinct tissue-specific requirements for WNT11 in outflow tract and DMP development.

MATERIALS
Product Number
Brand
Product Description

Sigma-Aldrich
Monoclonal Anti-α-Actinin (Sarcomeric) antibody produced in mouse, clone EA-53, ascites fluid
Sigma-Aldrich
Nuclear Fast Red Solution
Sigma-Aldrich
Eosin Y Solution, Alcoholic
Sigma-Aldrich
Hematoxylin Solution, Gill No. 1