Foucher Isabelle, Mione Marina, Simeone Antonio, Acampora Dario, Bally-Cuif Laure, Houart Corinne
MRC Centre for Developmental Neurobiology, New Hunt's House, King's College London, London SE1 9RT, UK.
Development. 2006 May;133(10):1891-900. doi: 10.1242/dev.02352. Epub 2006 Apr 12.
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.
尽管分泌分子Fgf8是峡部组织者功能的关键参与者，但其作用机制仍不清楚。在这里，我们提供的证据表明，Fgf8在建立斑马鱼小脑细胞身份方面并无指导作用，尽管它是该区域增殖和形态发生所必需的。我们首先表明，与小鼠一样，斑马鱼中Otx功能的缺失会导致假定的中脑转化为扩展的菱脑节1（r1）。Fgf8表达的扩展被认为是这种命运转变的原因。然而，本报告表明，同时缺乏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。我们表明，这不是由其他Fgf的存在引起的，这意味着在没有Otx的情况下，Fgf功能对于小脑细胞类型的分化不是必需的。因此，Otx蛋白是小脑命运的有效抑制因子，通过Fgf8排除在r1后代之外。由于在fgf8表达之前，假定的r1区域中不存在Otx转录本，因此需要Fgf8来维持而不是诱导Otx表达的后边界。这种维持足以允许小脑分化。
