Stubbs Jennifer L, Oishi Isao, Izpisúa Belmonte Juan Carlos, Kintner Chris
The Salk Institute for Biological Studies, San Diego, CA 92186, USA.
Nat Genet. 2008 Dec;40(12):1454-60. doi: 10.1038/ng.267. Epub 2008 Nov 16.
It has been proposed that ciliated cells that produce a leftward fluid flow mediate left-right patterning in many vertebrate embryos. The cilia on these cells combine features of primary sensory and motile cilia, but how this cilia subtype is specified is unknown. We address this issue by analyzing the Xenopus and zebrafish homologs of Foxj1, a forkhead transcription factor necessary for ciliogenesis in multiciliated cells of the mouse. We show that the cilia that underlie left-right patterning on the Xenopus gastrocoel roof plate (GRP) and zebrafish Kupffer's vesicle are severely shortened or fail to form in Foxj1 morphants. We also show that misexpressing Foxj1 is sufficient to induce ectopic GRP-like cilia formation in frog embryos. Microarray analysis indicates that Xenopus Foxj1 induces the formation of cilia by upregulating the expression of motile cilia genes. These results indicate that Foxj1 is a critical determinant in the specification of cilia used in left-right patterning.
有人提出,产生向左液体流动的纤毛细胞在许多脊椎动物胚胎中介导左右模式形成。这些细胞上的纤毛兼具初级感觉纤毛和运动纤毛的特征,但这种纤毛亚型是如何被特化的尚不清楚。我们通过分析小鼠多纤毛细胞中纤毛发生所必需的叉头转录因子Foxj1的非洲爪蟾和斑马鱼同源物来解决这个问题。我们发现,非洲爪蟾原肠腔顶板(GRP)和斑马鱼库普弗囊泡上作为左右模式形成基础的纤毛在Foxj1 morphants中严重缩短或无法形成。我们还表明,在青蛙胚胎中错误表达Foxj1足以诱导异位GRP样纤毛形成。微阵列分析表明,非洲爪蟾Foxj1通过上调运动纤毛基因的表达来诱导纤毛形成。这些结果表明,Foxj1是左右模式形成中所用纤毛特化的关键决定因素。