Elsevier

Developmental Biology

Volume 429, Issue 1, 1 September 2017, Pages 249-259
Developmental Biology

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

https://doi.org/10.1016/j.ydbio.2017.06.021Get rights and content
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Highlights

  • WNT11 is required for outflow tract and DMP development.

  • Outflow tract development requires myocardial WNT11 expression.

  • DMP development requires expression of WNT11 in Isl1Cre lineages.

  • DMP hypoplasia in Wnt11 mutants is correlated with reduced proliferation.

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.

Keywords

Wnt11
Heart
Outflow tract
Dorsal mesenchymal protrusion

Cited by (0)

1

Equal contribution.

2

Present address: CHU Sainte Justine Research Center, Montréal, Canada.