正确的心脏发育对胎儿和成年生活至关重要。各种信号通路的中断导致先天性心脏缺陷,包括流出道和流入道缺陷。我们以前发现WNT11调节流出道的发育。然而,在此过程中对WNT11的组织特定要求仍然未知,并且尚未解决流入道发育是否需要WNT11。在这里,我们发现种系Wnt11空小鼠也显示背侧间充质突起(DMP)的发育不全,这是房室间隔所必需的。在种系Wnt11空小鼠中观察到心肌cTnTCre重现的流出道缺陷的Wnt11消融,但是DMP的开发没有受到影响。相比之下,用Isl1Cre消融Wnt11完全概括了Wnt11种系空位的流出道和DMP缺陷。Wnt11突变体的DMP发育不全与DMP内增殖减少有关,但DMP的心肌分化无明显缺陷。检查Pitx2-,Axin2-,或Patched-lacZ报告小鼠显示报告表达没有改变,这表明需要WNT11的下游,或者平行于,这些信号通路调节DMP的形成。这些研究揭示了WNT11在DMP形成中的作用以及WNT11在流出道和DMP发育中的不同组织特异性要求。
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.