Neurite extension in central neurons: a novel role for the receptor tyrosine kinases Ror1 and Ror2

Abstract

Neurite elongation and branching are key cellular events during brain development as they underlie the formation of a properly wired neuronal network. Here we report that the receptor tyrosine kinases Ror1 and Ror2 modulate the growth of neurites as well as their branching pattern in hippocampal neurons. Upon Ror1 or Ror2 suppression using antisense oligonucleotides or RNA interference (RNAi), neurons extended shorter and less branched minor processes when compared to those in control cells. In addition, Ror-depleted cells elongated longer, albeit less branched, axons than seen in control cells. Conversely, Ror overexpression both in non-neuronal cells and in hippocampal neurons resulted in the enhanced extension of short and highly branched processes. These phenotypes were accompanied by changes in the microtubule-associated proteins MAP1B and MAP2. Taken together, these results support a novel role for Ror receptors as modulators of neurite extension in central neurons.

Canonical and noncanonical Wnt signaling in neural stem/progenitor cells

“…Neural tube defects in KO mice [96] Neural tube defects in VANGL1/2 DKO mice [78] VANGL2 Neural tube defects in KO mice [97] Neural tube defects in VANGL1/2 DKO mice [78] Causes precocious differentiation of neural progenitors into early-born neurons [79] Regulates asymmetric division in mouse SVZ [72] ROR1/2 Implicated in neurite extension [98] Implicated in synapse formation [99] Regulates differentiation in primary mouse neural progenitors…”

RoR2 functions as a noncanonical Wnt receptor that regulates NMDAR-mediated synaptic transmission

“…RoR2 receptors have been implicated in multiple aspects of brain development in Caenorhabditis elegans and Xenopus laevis, where they have been associated with Wnt5a signaling (18,19). Although they have been detected in mammalian cultured neurons (20), their function beyond embryonic development, i.e., in the regulation of established synaptic connections, is not known.…”

“…Although RoR2 protein has been detected in mammalian neurons (20), its function and signaling pathways are not known. Here we show that RoR2 acts as a receptor for noncanonical Wnt ligands capable of regulating synaptic NMDARs.…”

Effects of PAMAM dendrimers with various surface functional groups and multiple generations on cytotoxicity and neuronal differentiation using human neural progenitor cells

“…Our previous study about effects of thalidomide on the neural differentiation in hNPCs also demonstrated a promising model for neuronal development toxicity testing in vitro (Qin et al, 2012). For biological markers of neurodevelopmental toxicities, it has been reported that receptor tyrosine kinase-like orphan receptor 1 (Ror1) modulates the growth of neurites and their branching pattern in hippocampal neurons (Paganoni and Ferreira, 2005). The elevated levels of transforming growth factor, beta 1 (TGFB1) in ageing and neurodegenerative diseases have also been demonstrated (Kandasamy et al, 2014).…”