Sonic hedgehog maintains proliferation in secondary heart field progenitors and is required for normal arterial pole formation.
Sonic hedgehog maintains proliferation in secondary heart field progenitors and is required for normal arterial pole formation.
复制标题
Sonic Hedgehog在继发性心脏场祖细胞中保持增殖，是正常动脉极形成所必需的。
DOI：
10.1016/j.ydbio.2009.03.028
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发表时间：
2009-06-15
影响因子：
2.7
通讯作者：
Kirby, Margaret L.
中科院分区：
文献类型：
--
作者：
Dyer, Laura A.;Kirby, Margaret L.
The Sonic hedgehog (Shh)-null mouse was initially described as a phenotypic mimic of Tetralogy of Fallot with pulmonary atresia; however, subsequent reports describe only a single outflow tract, leaving the phenotype and its developmental mechanism unclear. We hypothesized that the phenotype that occurs in response to Shh knockdown is pulmonary atresia and is directly related to the abnormal development of the secondary heart field. We found that Shh was expressed by the pharyngeal endoderm adjacent to the secondary heart field and that its receptor Ptc2 was expressed in a gradient in the secondary heart field, with the most robust expression in the caudal secondary heart field, closest to the Shh expression. In vitro culture of secondary heart field with the hedgehog inhibitor cyclopamine significantly reduced proliferation. In ovo, cyclopamine treatment before the secondary heart field adds to the outflow tract reduced proliferation only in the caudal secondary heart field, which coincided with the region of high Ptc2 expression. After outflow tract septation should occur, embryos treated with cyclopamine exhibited pulmonary atresia, pulmonary stenosis, and persistent truncus arteriosus. Cardiac neural crest-derived cells, which form the outflow tract septum, migrated into the outflow tract and formed a septum. However, this septum divided the outflow tract into two unequal sized vessels and effectively closed off the pulmonary outlet. These experiments show that Shh is necessary for secondary heart field proliferation, which is required for normal pulmonary trunk formation, and that embryos with pulmonary atresia have an outflow tract septum.
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