Gβ2 Regulates the Multipolar-Bipolar Transition of Newborn Neurons in the Developing Neocortex

Proper neuronal migration is critical for the formation of the six-layered neocortex in the mammalian brain. However, the precise control of neuronal migration is not well understood. Heterotrimeric guanine nucleotide binding proteins (G proteins), composed of G alpha and G beta gamma, transduce signals from G protein-coupled receptors to downstream effectors and play crucial roles in brain development. However, the functions of individual subunits of G proteins in prenatal brain development remain unclear. Here, we report that G beta 2 is expressed in the embryonic neocortex, with abundant expression in the intermediate zone, and is significantly upregulated in differentiated neurons. Perturbation of G beta 2 expression impairs the morphogenetic transformation of migrating neurons from multipolar to bipolar and subsequently delays neuronal migration. Moreover, G beta 2 acts as a scaffold protein to organize the MP1-MEK1-ERK1/2 complex and mediates the phosphorylation of ERK1/2. Importantly, expression of a constitutively active variant of MEK1 rescues the migration defects that are caused by the loss of G beta 2. In conclusion, our findings reveal that G beta 2 regulates proper neuronal migration during neocortex development by activating the ERK1/2 signaling pathway.