Wnt4 is essential to normal mammalian lung development.
Wnt4 is essential to normal mammalian lung development.
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DOI：
10.1016/j.ydbio.2015.08.017
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发表时间：
2015-10-15
影响因子：
2.7
通讯作者：
Cleaver O
中科院分区：
文献类型：
--
作者：
Caprioli A;Villasenor A;Wylie LA;Braitsch C;Marty-Santos L;Barry D;Karner CM;Fu S;Meadows SM;Carroll TJ;Cleaver O
Wnt信号对器官发生过程中的许多事件至关重要，包括哺乳动物肺的发育。Wnt家族成员Wnt4已被证明是肾脏、性腺、胸腺、乳腺和垂体发育所必需的。在这里，我们发现Wnt4对呼吸系统的正常形态发生和生长至关重要。利用小鼠胚胎的原位杂交，我们在前干中胚层中发现了一个以前未被表征的Wnt4表达位点。该表达域最早在E8.25开始于靠近气管食管内胚层、融合背主动脉和心脏之间的中胚层。分析Wnt4−/−胚胎显示严重的肺发育不全和气管异常；然而，主动脉融合和食管发育不受影响。我们发现Wnt4−/−肺芽中细胞增殖减少，特别是在尖端区域。此外，在器官发生早期，我们观察到肺芽中重要的肺生长因子Fgf9、Fgf10、Sox9和Wnt2的减少，以及气管中祖因子Sox9的表达减少。总之，这些数据揭示了分泌蛋白Wnt4在呼吸系统发育中的未知作用。
Wnt signaling is essential to many events during organogenesis, including the development of the mammalian lung. The Wnt family member Wnt4 has been shown to be required for the development of kidney, gonads, thymus, mammary and pituitary glands. Here, we show that Wnt4 is critical for proper morphogenesis and growth of the respiratory system. Using in situ hybridization in mouse embryos, we identify a previously uncharacterized site of Wnt4 expression in the anterior trunk mesoderm. This expression domain initiates as early as E8.25 in the mesoderm abutting the tracheoesophageal endoderm, between the fusing dorsal aortae and the heart. Analysis of Wnt4−/− embryos reveals severe lung hypoplasia and tracheal abnormalities; however, aortic fusion and esophageal development are unaffected. We find decreased cell proliferation in Wnt4−/− lung buds, particularly in tip domains. In addition, we observe reduction of the important lung growth factors Fgf9, Fgf10, Sox9 and Wnt2 in the lung bud during early stages of organogenesis, as well as decreased tracheal expression of the progenitor factor Sox9. Together, these data reveal a previously unknown role for the secreted protein Wnt4 in respiratory system development.
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DOI：
10.1073/pnas.0902274106
发表时间：
2009-09-22
影响因子：
11.1
作者：
Harris-Johnson, Kelley S.;Domyan, Eric T.;Sun, Xin
通讯作者：
Sun, Xin
影响因子：
10.5
作者：
Akiyama, H;Chaboissier, MC;de Crombrugghe, B
通讯作者：
de Crombrugghe, B
影响因子：
20.3
作者：
Heinonen, Krista M.;Vanegas, Juan Ruiz;Perreault, Claude
通讯作者：
Perreault, Claude
影响因子：
3.7
作者：
Al Alam D;Green M;Tabatabai Irani R;Parsa S;Danopoulos S;Sala FG;Branch J;El Agha E;Tiozzo C;Voswinckel R;Jesudason EC;Warburton D;Bellusci S
通讯作者：
Bellusci S
影响因子：
158.5
作者：
Biason-Lauber, A;Konrad, D;Schoenle, EJ
通讯作者：
Schoenle, EJ