Formin-2 in establishing the spinal neuronal trajectory

Abstract

The proper functioning of a mature nervous system depends on the complex neuronal circuits. One of the critical phases of neuronal development is the formation of specific connections between the neurons and their target. The growth cone at the distal tip helps the axon to navigate through a pool of guidance cues. Growth cone contain a large amount of dynamic cytoskeletal elements and its motility is dependent on the polymerization of actin. Several factors control the dynamics of actin polymerization. Actin nucleators can increase the rate of addition of G-monomers to the actin filament and can nucleate the formation of a new filament. Actin nucleators are also required for cue mediated directional motility. Studies in our lab has shown the presence of the actin nucleators such as Fmn2 and Spire2, in the developing spinal cord. Cultured neurons showed decreased filopodia number and length and unstable focal adhesions, when the Fmn2 was depleted. This project primarily studied the role of Fmn2 in dI1 commissural neurons. Fmn2 depleted dI1 commissural neurons showed midline crossing defects. When mFmn2 was expressed specifically in the dI1 neurons, in the background of gFmn2 knockdown, the dI1 axons crossed the midline similar to the wild type. The rescue by mFmn2 underscores the evolutional conserved nature of Fmn2 function in the dI1 neurons as the mouse ortholog is able to rescue axon guidance of these neurons in the chick spinal cord. Expression of gFmn2 N terminal fragment also caused midline crossing defects in dI1 commissural neurons.