Neuropilin-1 biases dendrite polarization in the retina

Abstract

SUMMARYThe majority of neurons in the nervous system exhibit a polarized morphology, with multiple short dendrites and a single long axon. It is clear that multiple factors govern polarization in developing neurons, and the biased accumulation of intrinsic determinants to one side of the cell, coupled with responses to asymmetrically localized extrinsic factors, appears to be crucial. A number of intrinsic factors have been identified, but surprisingly little is known about the identity of the extrinsic signals. Here, we show in vivo that neuropilin-1 (Nrp1) and its co-receptor plexinA1 (Plxna1) are necessary to bias the extension of the dendrites of retinal ganglion cells to the apical side of the cell, and ectopically expressed class III semaphorins (Sema3s) disrupt this process. Importantly, the requirement for Nrp1 and Plxna1 in dendrite polarization occurs at a developmental time point after the cells have already extended their basally directed axon. Thus, we propose a novel mechanism whereby an extrinsic factor, probably a Sema3, acts through Nrp1 and Plxna1 to promote the asymmetric outgrowth of dendrites independently of axon polarization.

Changes in expression of Class 3 Semaphorins and their receptors during development of the rat retina and superior colliculus

“…Semaphorins (Semas) have been implicated in neural and vascular aspects of visual system development in various species including frog [8],[9], zebrafish [10]–[14], goldfish [15], and chicken [16]–[21]. In mouse the membrane bound Class 5 and Class 6 Semaphorins are involved in lamination of the retina [22]–[24], and guidance of retinal ganglion cell (RGC) axons [25] via contact-mediated interactions.…”

Mobilizing Endogenous Stem Cells for Retinal Repair

“…Among these factors, injury-induced inhibitory molecules, such as chondroitin sulfate proteoglycans, neurocan, hyaluronanbinding glycoprotein CD44, semaphorins and ephrins, are particularly abundant in the retina [77][78][79][80] . These molecules have previously been shown to function as inhibitory cues for neurite and axonal extension and block the regeneration of nerve fibers as well as neural stem cell growth 78,81 .…”

Semaphorins and the dynamic regulation of synapse assembly, refinement, and function

“…In the Xenopus retina, class 3 semaphorins regulate asymmetric growth of retinal ganglion cell (RGC) dendritic arbors [10]. In the mouse retina, the transmembrane semaphorins Sema6A, Sema5A and Sema5B direct precise neurite patterning of select retinal cell types [11,12,13].…”