Topp Stefanie, Stigloher Christian, Komisarczuk Anna Z, Adolf Birgit, Becker Thomas S, Bally-Cuif Laure
Helmholtz Zentrum muenchen, German Research Center for Environmental Health, Department Zebrafish Neurogenetics, Institute of Developmental Genetics, D-85764 Neuherberg, Germany.
J Comp Neurol. 2008 Oct 1;510(4):422-39. doi: 10.1002/cne.21802.
The zebrafish adult brain contains numerous neural progenitors and is a good model to approach the general mechanisms of adult neural stem cell maintenance and neurogenesis. Here we use this model to test for a correlation between Fgf signaling and cell proliferation in adult progenitor zones. We report expression of Fgf signals (fgf3,4,8a,8b,17b), receptors (fgfr1-4), and targets (erm, pea3, dusp6, spry1,2,4, and P-ERK) and document that genes of the embryonic fgf8 synexpression group acquire strikingly divergent patterns in the adult brain. We further document the specific expression of fgf3, fgfr1-3, dusp6, and P-ERK in ventricular zones, which contain neural progenitors. In these locations, however, a comparison at the single-cell level of fgfr/P-ERK expression with bromo-deoxy-uridine (BrdU) incorporation and the proliferation marker MCM5 indicates that Fgf signaling is not specifically associated with proliferating progenitors. Rather, it correlates with the ventricular radial glia state, some of which only are progenitors. Together these results stress the importance of Fgf signaling in the adult brain and establish the basis to study its function in zebrafish, in particular in relation to adult neurogenesis.
成年斑马鱼的大脑含有大量神经祖细胞，是研究成年神经干细胞维持和神经发生一般机制的良好模型。在这里，我们使用这个模型来测试成年祖细胞区中Fgf信号与细胞增殖之间的相关性。我们报告了Fgf信号（fgf3、4、8a、8b、17b）、受体（fgfr1 - 4）和靶标（erm、pea3、dusp6、spry1、2、4和P - ERK）的表达，并记录了胚胎期fgf8共表达组的基因在成年大脑中呈现出显著不同的模式。我们进一步记录了fgf3、fgfr1 - 3、dusp6和P - ERK在包含神经祖细胞的脑室区的特异性表达。然而，在这些位置，在单细胞水平上比较fgfr/P - ERK表达与溴脱氧尿苷（BrdU）掺入以及增殖标记物MCM5表明，Fgf信号与增殖祖细胞并无特异性关联。相反，它与脑室放射状胶质细胞状态相关，其中只有一部分是祖细胞。这些结果共同强调了Fgf信号在成年大脑中的重要性，并为研究其在斑马鱼中的功能，特别是与成年神经发生相关的功能奠定了基础。
