Functional analysis of neuronal IgCAMs in c. elegans

大脑是最迷人的器官之一。在发育过程中，单个神经元向目标发出长达很长距离的过程，在那里它们与目标神经元建立联系，最终形成神经元回路。细胞-细胞黏附和细胞-底物黏附现象在神经元发育的各个方面发挥着重要作用，但人们对此知之甚少。在神经系统发育中起重要作用的最大的细胞黏附受体家族是免疫球蛋白细胞黏附分子(IgCAMs)。对各种动物的基因组测序揭示了这些家族的所有成员。关于它们的功能，到目前为止，只有一小部分基因被确定了特征。有了这个提议，我们想要开始对大脑中发现的那些IgCAM超家族成员进行功能分析。我们将在线虫中产生这些基因的有针对性的敲除，并确定它们参与的发育过程。将这种分析从单基因水平扩展到基因家族水平的能力使我们能够确定这些家族成员之间的功能冗余，这是一个以前在没有所有家庭成员完全了解的情况下很难解决的问题。这些黏附分子家族的进化保守性使我们能够得出关于这个家族对神经元发育的贡献的一般结论，脊椎动物也是如此。

The brain is one of the most fascinating organs. During its development individual neurons send out processes which grow over large distances to their targets, where they establish contacts with target neurons to eventually form neuronal circuits. Cell-cell adhesion and cell-substrate adhesion phenomena play an important role in various aspects of neuronal development and are only poorly understood. The largest families of cell adhesion receptors with an established role in nervous system development are the immunoglobulin cell adhesion molecules (IgCAMs). Sequencing of the genomes of various animals revealed all the members of these families. With respect to their function only a fraction of these genes has been characterized so far. With this proposal we would like to initiate a functional analysis of those members of the IgCAM superfamily that are found in the brain. We will generate targeted knock-outs of those genes in the nematode C. elegans and determine the developmental process they are involved in. The ability to extend such an analysis from the single gene level to the gene family level allows us to determine functional redundancies among members of these families, an issue which was difficult to address before without the complete knowledge of all the family members. The evolutionary conservation of these families of adhesion molecules enables us to draw general conclusions about the contributions of this family to neuronal development also in vertebrates.