Differentiation of cerebellar cell identities in absence of Fgf signalling in zebrafish Otx morphants
Differentiation of cerebellar cell identities in absence of Fgf signalling in zebrafish Otx morphants
复制标题
DOI：
10.1242/dev.02352
复制
发表时间：
2006-05-15
期刊：
影响因子：
4.6
通讯作者：
Houart, C
中科院分区：
文献类型：
--
作者：
Foucher, I;Mione, M;Houart, C
尽管分泌分子Fgf8是峡部组织者功能的关键参与者，但它的作用机制尚不清楚。在这里，我们提出的证据表明，Fgf8在建立斑马鱼小脑细胞身份方面没有指导意义，尽管它是斑马鱼小脑细胞增殖和形态发生所必需的。我们首先证明，与小鼠一样，斑马鱼OTX功能的缺失会导致假定的中脑转变为扩展的菱形核1(R1)。扩展的Fgf8表达被认为是这种命运转变的原因。然而，这份报告表明，缺乏OTX和Fgf8功能的斑马鱼胚胎保留了扩展的R1，并显示出至少两种小脑细胞命运的分化。我们发现这不是由于其他FGFs的存在引起的，这意味着在没有OTX的情况下，成纤维细胞生长因子的功能不是小脑细胞类型分化所必需的。因此，OTX蛋白是小脑命运的有效抑制因子，被Fgf8排除在R1后代之外。由于OTX转录本在Fgf8表达之前不存在于假定的R1区域，Fgf8需要维持而不是诱导OTX表达的后边界。这种维持足以使小脑分化。
Although the secreted molecule Fgf8 is a key player of the isthmic organiser function, the mechanisms by which it acts remain unclear. Here, we present evidence indicating that Fgf8 is not instructive in establishing zebrafish cerebellar cell identities, although it is required for proliferation and morphogenesis of this territory. We first show that, as in mouse, lack of Otx function in zebrafish leads to transformation of the presumptive mesencephalon into an extended rhombomere 1 (r1). Expanded Fgf8 expression was proposed to be the cause of this fate transformation. However, this report demonstrates that zebrafish embryos lacking both Otx and fgf8 functions retain an extended r1 and display differentiation of at least two cerebellar cell fates. We show that this is not caused by presence of other Fgfs, which implies that in absence of Otx, Fgf function is not necessary for the differentiation of cerebellar cell types. Otx proteins are therefore potent repressors of cerebellar fates, kept out of r1 progeny by Fgf8. Because Otx transcripts are not present in presumptive r1 territory prior to fgf8 expression, Fgf8 is required to maintain, rather than induce, the posterior boundary of Otx expression. This maintenance is enough to allow cerebellar differentiation.