Wnt5a plays a critical role in anal opening in mice at an early stage of embryonic development
Wnt5a plays a critical role in anal opening in mice at an early stage of embryonic development
复制标题
DOI：
10.1007/s00383-022-05103-4
复制
发表时间：
2022-02-25
影响因子：
1.8
通讯作者：
Hishiki，Tomoro
中科院分区：
文献类型：
--
作者：
Nakata，Mitsuyuki;Honda，Hiroaki;Hishiki，Tomoro
目的肛门直肠畸形常合并其他器官畸形。泄殖腔板的近远侧延长和远端肛门开口是肛门发育所必需的。然而，Wnt 5直接参与的肛门发育阶段仍不清楚。在这里，我们试图确定这一发展阶段，sinceWnt 5ais中胚层表达，和小鼠中的横纹肌复合体（SMC）中胚层的发展，我们还研究了Wnt 5a的贡献SMC development.MethodsWe建立条件性基因敲除（CKO）小鼠，其中Wnt 5acould敲除使用适当的他莫昔芬剂量。结果在E8-E11期敲除Wnt 5a后，Wnt 5aCKO小鼠表现出典型的Wnt 5基因敲除小鼠表型。此外，当Wnt 5a在E8时被敲除时，肛门不能打开，但当其在E9或之后被敲除时，肛门打开。尾部末端的SMC发育不良的Wnt 5aCKO小鼠诱导E8，但不受影响，当小鼠诱导E9或afterno.ConclusionWe建议一个关键的作用forWnt 5ain肛门开放和SMC形成在胚胎发育的早期阶段。
PurposeAnorectal malformations are associated with other organ malformations. Proximodistal elongation of the cloacal plate and anal opening at its distal end are essential for anal development. However, the anal developmental stage in whichWnt5ais directly involved remains unelucidated. Here, we attempted to identify this developmental stage; sinceWnt5ais expressed in the mesoderm, and the striated muscle complex (SMC) in mice develops from the mesoderm, we also examined Wnt5a contribution to SMC development.MethodsWe established conditional knockout (CKO) mice in whichWnt5acould be knocked out using an appropriate tamoxifen dose. We evaluated the macroscopic appearance and histopathological features of Wnt5aCKO and wild-type mouse embryos.ResultsWnt5aCKO mice showed phenotypes typical ofWnt5aconstitutional knockout mice whenWnt5awas knocked out at E8–E11. Furthermore, the anus failed to open whenWnt5awas knocked out at E8 but opened when it was knocked out at E9 or thereafter. The caudal end of the SMC was dysplastic in Wnt5aCKO mice induced at E8, but was unaffected when mice were induced at E9 or thereafter.ConclusionWe suggest a critical role forWnt5ain anal opening and SMC formation at a very early stage of embryonic development.