Analysis of FLRT family proteins as novel axon guidance molecules

哺乳动物排斥性Netrin受体的Unc 5家族包括四个直向同源物（Unc 5A-D），其功能尚不清楚。在发育中的新皮质中，以Unc 5D表达为特征的室下区（SVZ）中的神经元亚群显示延迟迁移至皮质板（CP）。然而，这种行为的潜在机制尚不清楚。Unc 5D被证明可以结合纤连蛋白和富含亮氨酸的跨膜蛋白-3（FLRT 3），但其相关性尚不清楚。我们表明，FLRT 2，这是在CP中表达，是一个新的Unc 5D配体。在FLRT 2或Unc 5D突变体中，SVZ神经元的亚群显示出向CP的过早迁移，而Unc 5D过表达具有相反的效果。这些发现表明，FLRT 2代表了一种排斥性引导线索，导致Unc 5D+神经元在开始迁移之前长时间驻留在SVZ中。

The mammalian Unc5 family of repulsive Netrin receptors comprises four orthologues (Unc5A-D) whose functions are not well understood. In the developing neocortex, a subpopulation of neurons in the subventricular zone (SVZ) characterized by the expression of Unc5D, displays delayed migration to the cortical plate (CP). However, the underlying mechanism of this behavior is unknown. Unc5D was shown to bind Fibronectin and leucine-rich transmembrane protein-3 (FLRT3), the relevance of which is unclear. We show that FLRT2, which is expressed in the CP, is a new ligand for Unc5D. In FLRT2 or Unc5D mutants, a subpopulation of SVZ neurons shows premature migration towards the CP, whereas Unc5D overexpression has opposite effects. These findings suggest that FLRT2 represents a repulsive guidance cue that causes Unc5D+ neurons to reside in the SVZ for a prolonged period before initiating migration.