IQGAP1 Regulates Adult Neural ProgenitorsIn Vivoand Vascular Endothelial Growth Factor-Triggered Neural Progenitor MigrationIn Vitro

Abstract

In the germinative zone of the adult rodent brain, neural progenitors migrate into niches delimited by astrocyte processes and differentiate into neuronal precursors. In the present study, we report a modulating role for the scaffolding protein IQGAP1 in neural progenitor migration. We have identified IQGAP1 as a new marker of amplifying neural progenitor and neuronal precursor cells of the subventricular zone (SVZ) and the rostral migratory stream (RMS) in the adult mouse brain. To determine functions for IQGAP1 in neural progenitors, we compared the properties of neural progenitor cells from wild-type and Iqgap1-null mutant mice in vivo and in vitro. The in vivo studies reveal a delay in the transition of de novo neural progenitors into neuronal precursor cells in Iqgap1-null mice. In vitro, we demonstrated that IQGAP1 acts as a downstream effector in the vascular endothelial growth factor (VEGF)-dependent migratory response of neural progenitors that also impacts on their neuronal differentiation. The Rho-family GTPases cdc42/Rac1 and Lis1 are major partners of IQGAP1 in this migratory process. Finally, astrocytes of the neurogenic SVZ and RMS are shown to express VEGF. We propose that VEGF synthesized by astrocytes could be involved in the guidance of neural progenitors to neurogenic niches and that IQGAP1 is an effector of the VEGF-dependent migratory signal.

RalA promotes a direct exocyst-Par6 interaction to regulate polarity in neuronal development

“…This might seem surprising; however, based on our data the Exo84 internal PDZbinding motif is not required for exocyst complex association. In the RMS, RalA-promoted exocyst assembly might serve multiple functions, such as the polarized delivery of integrins (Spiczka and Yeaman, 2008) and matrix metalloproteinases (Liu et al, 2009), which can regulate migration along the RMS (Murase and Horwitz, 2002;Belvindrah et al, 2007;Bovetti et al, 2007), and the recruitment of IQGAP1 (Sakurai-Yageta et al, 2008), a signaling scaffold protein involved in neuroblast migration (Balenci et al, 2007). In addition, our single-end-point assay in fixed brain slices, which can detect strong migration phenotypes, might lack the sensitivity needed to uncover subtler defects in cell dynamics.…”

VEGFR-1 Regulates Adult Olfactory Bulb Neurogenesis and Migration of Neural Progenitors in the Rostral Migratory Stream In Vivo

“…VEGF-A is a member of the VEGF family that includes six different homologous factors: VEGF-A-VEGF-E and placental growth factor (Raab and Plate, 2007). VEGF-A is expressed by glial cells within the SVZ and the RMS (Balenci et al, 2007). VEGF-A functions by binding to the receptor tyrosine kinases VEGF receptor-1 (VEGFR-1) [fmsrelated tyrosine kinase-1 (Flt-1)] (Shibuya et al, 1990;de Vries et al, 1992) and VEGF receptor-2 (VEGFR-2) (fetal liver kinase 1) (Terman et al, 1991).…”

“…VEGF-A functions by binding to the receptor tyrosine kinases VEGF receptor-1 (VEGFR-1) [fmsrelated tyrosine kinase-1 (Flt-1)] (Shibuya et al, 1990;de Vries et al, 1992) and VEGF receptor-2 (VEGFR-2) (fetal liver kinase 1) (Terman et al, 1991). In vitro VEGFR-2 has been shown to transmit VEGF-A-mediated response in neural cells (Cao et al, 2004;Schänzer et al, 2004;Balenci et al, 2007). Furthermore VEGFR-2 signaling directly modulates behavior of retinal progenitor cells (Hashimoto et al, 2006).…”

Neural Stem Cells: Exogenous and Endogenous Promising Therapies for Stroke

“…VEGF expression is observed in astrocytes, being higher in astrocytes of the SVZ and RMS than in astrocytes from non-permissive regions (Balenci et al, 2007). This expression represents an endogenous source of VEGF that can be related to neurogenesis and might have a direct effect on the migration of neural progenitors within neurogenic regions (Balenci et al, 2007).…”

“…In vivo, intraventricular VEGF administration revealed that VEGFR2/Flk-1 receptors predominate in neurogenic niches such as the SVZ and co-localize with migrating neuroblasts as well as astroglial, endothelial and neuronal cells (Jin et al, 2002;Schänzer et al, 2004). VEGF expression is observed in astrocytes, being higher in astrocytes of the SVZ and RMS than in astrocytes from non-permissive regions (Balenci et al, 2007). This expression represents an endogenous source of VEGF that can be related to neurogenesis and might have a direct effect on the migration of neural progenitors within neurogenic regions (Balenci et al, 2007).…”