Abnormal Neuronal Migration Changes the Fate of Developing Neurons in the Postnatal Olfactory Bulb

Abstract

Neuronal precursors are continuously integrated into the adult olfactory bulb (OB).

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

“…Indeed, perturbing the RalA-Exo84 interaction significantly disrupted the final distribution of newborn neurons in the OB (Fig. 5), which is likely to affect their fate and synaptic integration, as in the case of another migration regulator, doublecortin (Belvindrah et al, 2011). RMS neuroblast migration is saltatory, alternating process extension with nucleokinesis, with a very dynamic leading protrusion (Nam et al, 2007;Sonego et al, 2013b).…”

“…This evidence, together with the defects caused by siRNA-mediated RalA depletion in vitro and by expression of inactive or exocyst-uncoupled RalA mutants in vivo, strongly supports a role for this small GTPase in regulating neuroblast morphology and polarity. This might have important implications for the maturation of neuroblasts into neurons (Belvindrah et al, 2011;Sanai et al, 2011) and for their ability to re-route to injured brain areas (Arvidsson et al, 2002;SundholmPeters et al, 2005). Potential modulators of RalA activity in migrating neuroblasts could be cell adhesion molecules, such as N-cadherin or integrins, which are enriched in the RMS (Yagita et al, 2009;Kazanis et al, 2010) and have been linked to RalA activation in other systems (Lalli and Hall, 2005;Jossin and Cooper, 2011).…”

“…SVZ stem cells generate neuroblasts that move rostrally, forming the 'rostral migratory stream' (RMS), towards the olfactory bulb (OB), where they differentiate into inhibitory interneurons (Luskin, 1993;Lois and Alvarez-Buylla, 1994;Doetsch and Alvarez-Buylla, 1996;Lledo et al, 2006). This polarized migration is crucial for postnatal neurogenesis, controlling the fate and integration of new neurons into a preexisting synaptic network (Belvindrah et al, 2011).…”

Speed control for neuronal migration in the postnatal brain by Gmip-mediated local inactivation of RhoA

“…The opposite direction was defined as 180°. GFP þ cells with the longest leading process extending in a direction within a 30°angle on either side of 0°towards the OB were defined as forward-directed cells (described as 'forward'), those within a 30°angle on either side of 180°were defined as reverse-directed cells (described as 'reverse'), and those in all other directions were designated as 'others,' as previously reported 19,54,55 . To quantify the number of GFP þ BrdU þ Dcx þ cells or GFP þ BrdU þ cleaved caspase-3 þ cells in the V-SVZ and RMS ( Supplementary Fig.…”

“…The speed of migration in the RMS is about twice that of the radial glia fiberguided migration of cortical neurons 18 . Altering the speed of migration in the RMS can affect the fate of newborn OB neurons 19 . Previous studies have shown that this complex neuronal migration is regulated through the orchestrated activities of multiple signals.…”