Ion channels, guidance molecules, intracellular signaling and transcription factors regulating nervous and vascular system development

Abstract

Our sophisticated thoughts and behaviors are based on the miraculous development of our complex nervous network system, in which many different types of proteins and signaling cascades are regulated in a temporally and spatially ordered manner. Here we review our recent attempts to grasp the principles of nervous system development in terms of general cellular phenomena and molecules, such as volume-regulated anion channels, intracellular Ca2+ and cyclic nucleotide signaling, the Npas4 transcription factor and the FLRT family of axon guidance molecules. We also present an example illustrating that the same FLRT family may regulate the development of vascular networks as well. The aim of this review is to open up new vistas for understanding the intricacy of nervous and vascular system development.

Epigenetically regulated Fibronectin leucine rich transmembrane protein 2 (FLRT2) shows tumor suppressor activity in breast cancer cells

“…FLRT proteins are known to interact with several other proteins, such as ROBO1 17 , LPHN3 and UNC5 18, 19 . Through these interactions, FLRTs function as ribonuclease inhibitors 20 , virulence factors 21 , or splicing mediators 22 .…”

“…FLRT2 (Fibronectin leucine rich transmembrane protein 2) is a member of the FLRT family proteins, which contain 10 LRR (leucine-rich repeats) domains and a transmembrane domain 16 . FLRT proteins are known to interact with several other proteins, such as ROBO1 17 , LPHN3 and UNC5 18 , 19 . Through these interactions, FLRTs function as ribonuclease inhibitors 20 , virulence factors 21 , or splicing mediators 22 .…”

An extracellular biochemical screen reveals that FLRTs and Unc5s mediate neuronal subtype recognition in the retina

“…Some interactions among these molecules have previously been described ( Karaulanov et al, 2009 ; Sollner and Wright, 2009 ; Yamagishi et al, 2011 ; Seiradake et al, 2014 ), while others are newly identified in our screen. Members of both the Unc5 and FLRT families exhibit multiple roles in development in a variety of different systems with various interaction partners ( Bottcher et al, 2004 ; Dakouane-Giudicelli et al, 2014 ; Finci et al, 2015 ; Akita et al, 2015 ). Using immunostaining and single cell ex vivo stripe assays, we found FLRTs and Unc5s exhibit distinct sublaminar expression patterns in the IPL and elicit repulsion and/or attraction in subsets of retinal neurons.…”

Extracellular NME proteins: a player or a bystander?

“…Indeed, chemotactic signals are broadly used during CNS development and, interestingly, evidence suggests that similar stimuli and subtended signaling pathways could also regulate vascular system development. 27 The exact mechanism through which Nme1 drives neurite outgrowth is not defined but the NDPK function seems not necessary, since extracellular kinase-dead mutant Nme1 H118F is able to induce the same effect as the wild type protein.…”