Institut de Recherches Cliniques de Montréal, Montréal, Québec, H2W 1R7, Canada.
J Neurosci. 2012 Jan 11;32(2):411-6. doi: 10.1523/JNEUROSCI.3563-11.2012.
Down syndrome cell adhesion molecule (DSCAM) has mainly been characterized for its function as an adhesion molecule in axon growth and in self-recognition between dendrites of the same neuron. Recently, it has been shown that DSCAM can bind to Netrin-1 and that downregulation of DSCAM expression by siRNAs in chick and rodent spinal cords leads to impaired growth and turning response of commissural axons to Netrin-1. To investigate the effect of complete genetic ablation of DSCAM on Netrin-1-induced axon guidance, we analyzed spinal commissural neurons in DSCAM-null mice and found that they extend axons that reach and cross the floor plate and express apparently normal levels of the Netrin receptors DCC (deleted in colorectal carcinoma) and Neogenin. In vitro, commissural neurons in dorsal spinal cord explants of DSCAM-null embryos show normal outgrowth in response to Netrin-1. We therefore conclude that DSCAM is not required for Netrin-induced commissural axon outgrowth and guidance in mice.
唐氏综合征细胞黏附分子（DSCAM）主要以其作为轴突生长中的黏附分子和同一神经元树突之间自我识别的功能而被描述。最近，已经表明 DSCAM 可以与 Netrin-1 结合，并且 chick 和 rodent 脊髓中的 siRNAs 下调 DSCAM 表达会导致联络轴突对 Netrin-1 的生长和转向反应受损。为了研究 DSCAM 完全遗传缺失对 Netrin-1 诱导的轴突导向的影响，我们分析了 DSCAM 缺失小鼠中的脊髓联络神经元，发现它们延伸的轴突到达并穿过基板，并明显表达正常水平的 Netrin 受体 DCC（结直肠癌缺失）和 Neogenin。在体外，DSCAM 缺失胚胎的背侧脊髓外植体中的联络神经元对 Netrin-1 表现出正常的生长。因此，我们得出结论，DSCAM 对于 Netrin 诱导的小鼠联络轴突生长和导向不是必需的。
