The Guanine Exchange FactorvavControls Axon Growth and Guidance duringDrosophilaDevelopment

Abstract

The Vav proteins are guanine exchange factors (GEFs) that trigger the activation of the Rho GTPases in general and the Rac family in particular. While the role of the mammalian vav genes has been extensively studied in the hematopoietic system and the immune response, there is little information regarding the role of vav outside of these systems. Here, we report that the single Drosophila vav homolog is ubiquitously expressed during development, although it is enriched along the embryonic ventral midline and in the larval eye discs and brain. We have analyzed the role that vav plays during development by generating Drosophila null mutant alleles. Our results indicate that vav is required during embryogenesis to prevent longitudinal axons from crossing the midline. Later on, during larval development, vav is required within the axons to regulate photoreceptor axon targeting to the optic lobe. Finally, we demonstrate that adult vav mutant escapers, which exhibit coordination problems, display axon growth defects in the ellipsoid body, a brain area associated with locomotion control. In addition, we show that vav interacts with other GEFs known to act downstream of guidance receptors. Thus, we propose that vav acts in coordination with other GEFs to regulate axon growth and guidance during development by linking guidance signals to the cytoskeleton via the modulation of Rac activity.

The vav oncogene antagonises EGFR signalling and regulates adherens junction dynamics during Drosophila eye development

“…We showed that vav is ubiquitously expressed in the eye disc, which is consistent with a possible function of Vav during eye development (Malartre et al, 2010).…”

“…5A,B). First, we confirmed that the GEF activity was compromised in these new DH point mutation alleles, as they all exhibited phenotypes similar to those of vav and Rac nulls during axonal targeting (Malartre et al, 2010; data not shown). Interestingly, these mutants also exhibited phenotypes similar to those associated with the vav-null alleles in the retina, with lower penetrance only for the single amino acid deletion (Fig.…”

“…S3B). Given that the vav and Rac phenotypes in the retina are different, as opposed to the similar axon guidance phenotypes they display (Malartre et al, 2010), Rac proteins are unlikely to be the main Vav effectors for regulating cell recruitment in the eye, suggesting that Vav uses distinct effectors to regulate eye patterning and axon targeting.…”

The GEF Vav regulates guided cell migration by coupling guidance receptor signalling to local Rac activation

“…We utilized two unrelated null alleles, vav 3 and vav 11837 (Malartre et al, 2010) that gave rise to indistinguishable phenotypes; however, in the text and in the figures we refer only to the results obtained with vav 3 . The migration phenotype was quantified typically by scoring S10 egg chambers, which is when wild-type BCs reach the oocyte and migration has been completed (Fig.…”

A Conserved GEF for Rho-Family GTPases Acts in an EGF Signaling Pathway to Promote Sleep-like Quiescence inCaenorhabditis elegans

“…Although the functions of Vav proteins in the nervous system are far from clear, several studies have found critical roles for Vav family members in nervous system function. For example, Vav proteins have been shown to be important for axonal development (Cowan et al 2005;Malartre et al 2010;Sauzeau et al 2010a;Fernandez-Espartero et al 2013), synaptic plasticity (Hale et al 2011), and negative regulation of sympathetic nervous system activity (Sauzeau et al 2006(Sauzeau et al , 2007(Sauzeau et al , 2010b(Sauzeau et al , 2011Zhu et al 2015). Moreover, Vav3 has been identified as a candidate schizophrenia gene (Ikeda et al 2011;Aleksic et al 2013).…”