Developing new tools for the application of site-specific recombinases in zebrafish

与哺乳动物相比，大多数非哺乳动物脊椎动物保留了在成年大脑的许多区域产生新神经元的能力。因此，鉴定成年斑马鱼脑中16个高度保守的增殖域，为我们理解维持成体干细胞活性的机制提供了重要的手段。然而，更好的理解需要一套不同的遗传工具。在小鼠中，像Cre这样的位点特异性重组酶已经成为干细胞研究不可或缺的资源。我们最近表明，Cre在斑马鱼中也是高效的。为了利用这一潜力，我们的目标是扩大条件Cre驱动系的库，并进行大规模的启动子和基因陷阱筛选，以分离在成人大脑不同区域表达Cre的新等位基因。此外，我们将使用翻转切除技术(FLEX)分离斑马鱼中目前无法获得的条件性基因敲除等位基因。这些结果应该会为操纵成年斑马鱼的大脑提供更好的工具，从而深入了解脊椎动物大脑中成年神经干细胞活动的机制。

In contrast to mammals, most non-mammalian vertebrates have retained the capacity to generate new neurons in many areas of the adult brain. Therefore, the identification of 16 highly conserved prolifera-tive domains in the adult zebrafish brain provides an important mean to our understanding of the me-chanisms that maintain adult stem cell activity. However, better understanding requires a different set of genetic tools. In mouse, site-specific recombinases like Cre have emerged as an indispensable resource for stem cell research. We recently showed that Cre is also highly efficient in zebrafish. In order to utilize this potential, we aim to expand the pool of conditional Cre driver lines and perform a large-scale promoter and gene trap screen to isolate novel alleles expressing Cre in different domains of the adult brain. Furthermore, we will use the flip-excision technology (FlEx) to isolate conditional knockout alleles which are currently unavailable in zebrafish. The results should provide better tools for the manipulation of the adult zebrafish brain and consequently insights into the mechanisms underlying adult neural stem cell activity in the vertebrate brain.