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 Gα and Gβγ, 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 Gβ2 is expressed in the embryonic neocortex, with abundant expression in the intermediate zone, and is significantly upregulated in differentiated neurons. Perturbation of Gβ2 expression impairs the morphogenetic transformation of migrating neurons from multipolar to bipolar and subsequently delays neuronal migration. Moreover, Gβ2 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 Gβ2. In conclusion, our findings reveal that Gβ2 regulates proper neuronal migration during neocortex development by activating the ERK1/2 signaling pathway.
Key Laboratory of Molecular Epigenetics, Ministry of Education and Institute of Cytology and Genetics, Northeast Normal University, Changchun 130024, China.
Ye
Y
Guo
Key Laboratory of Molecular Epigenetics, Ministry of Education and Institute of Cytology and Genetics, Northeast Normal University, Changchun 130024, China.
Xiaoxiao
X
He
Key Laboratory of Molecular Epigenetics, Ministry of Education and Institute of Cytology and Genetics, Northeast Normal University, Changchun 130024, China.
Lu
L
Zhao
Key Laboratory of Molecular Epigenetics, Ministry of Education and Institute of Cytology and Genetics, Northeast Normal University, Changchun 130024, China.
Lin
L
Liu
Key Laboratory of Molecular Epigenetics, Ministry of Education and Institute of Cytology and Genetics, Northeast Normal University, Changchun 130024, China.
Huifang
H
Song
Key Laboratory of Molecular Epigenetics, Ministry of Education and Institute of Cytology and Genetics, Northeast Normal University, Changchun 130024, China.
Xudong
X
Wang
Key Laboratory of Molecular Epigenetics, Ministry of Education and Institute of Cytology and Genetics, Northeast Normal University, Changchun 130024, China.
Jiahui
J
Xu
Key Laboratory of Molecular Epigenetics, Ministry of Education and Institute of Cytology and Genetics, Northeast Normal University, Changchun 130024, China.
Xingda
X
Ju
State Key Laboratory for Molecular and Developmental Biology, Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, Beijing 100101, China.
Weixiang
W
Guo
Key Laboratory of Molecular Epigenetics, Ministry of Education and Institute of Cytology and Genetics, Northeast Normal University, Changchun 130024, China.
Xiaojuan
X
Zhu
D048868:Adaptor Proteins, Signal Transducing / Q000378:metabolism; D000818:Animals; D002465:Cell Movement / Q000235:genetics; D016764:Cell Polarity / Q000502:physiology; D002478:Cells, Cultured; D005260:Female; D044387:GTP-Binding Protein beta Subunits / Q000235:genetics / Q000378:metabolism*; D018507:Gene Expression Regulation, Developmental / Q000235:genetics / Q000502:physiology*; D057809:HEK293 Cells; D006801:Humans; D020935:MAP Kinase Signaling System / Q000235:genetics; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D019579:Neocortex / Q000166:cytology* / Q000196:embryology*; D064231:Nestin / Q000378:metabolism; D058953:Neural Stem Cells / Q000502:physiology; D009474:Neurons / Q000502:physiology*; D010766:Phosphorylation / Q000235:genetics; D034741:RNA, Small Interfering / Q000235:genetics / Q000378:metabolism
D048868:Adaptor Proteins, Signal Transducing; D044387:GTP-Binding Protein beta Subunits; C114559:Lamtor3 protein, mouse; D064231:Nestin; D034741:RNA, Small Interfering
cerebral cortex development, ERK1/2, Gβ2, MP1, neuronal migration