Loss of ciliary transition zone protein TMEM107 leads to heterotaxy in mice.
Loss of ciliary transition zone protein TMEM107 leads to heterotaxy in mice.
复制标题
睫状过渡区蛋白 TMEM107 的缺失会导致小鼠异位。
DOI：
10.1016/j.ydbio.2019.12.014
复制
发表时间：
2020
影响因子：
2.7
通讯作者：
Weatherbee,ScottD
中科院分区：
文献类型：
--
作者：
Shylo,NataliaA;Emmanouil,Elli;Ramrattan,Dylan;Weatherbee,ScottD
在大多数脊椎动物的左右组织者中，纤毛参与了左右（L-R）对称性的原始破坏，然而，关于它们在级联反应的后续步骤中的作用-中继信号和维持既定的不对称性，人们知之甚少。在这里，我们描述了两个突变体的纤毛过渡区蛋白TMEM 107的L-R图案级联，揭示了近完全丧失纤毛在TMEM 107 null导致左肺异构由于中线屏障的失败。相反，部分保留的纤毛在节点和中线的hypomorphicTmem 107 schleimutant出现足够的中线屏障的形成和建立和维护的L-R不对称。尽管Shh信号在两种突变体中的错误调节，但Tmem 107突变体中正常Lefty 1表达和中线屏障形成的存在表明，Lefty 1表达和中线屏障形成需要纤毛，但Shh信号不一定需要。
Cilia in most vertebrate left-right organizers are involved in the original break in left-right (L-R) symmetry, however, less is known about their roles in subsequent steps of the cascade – relaying the signaling and maintaining the established asymmetry. Here we describe the L-R patterning cascades in two mutants of a ciliary transition zone protein TMEM107, revealing that near-complete loss of cilia inTmem107nullleads to left pulmonary isomerism due to the failure of the midline barrier. Contrary, partially retained cilia in the node and the midline of a hypomorphicTmem107schleimutant appear sufficient for the formation of the midline barrier and establishment and maintenance of the L-R asymmetry. Despite misregulation ofShhsignaling in both mutants, the presence of normalLefty1expression and midline barrier formation inTmem107schleimutants, suggests a requirement for cilia, but not necessarilyShhsignaling forLefty1expression and midline barrier formation.