AUTHOR=Gahankari Apurva , Dong Chunmin , Bartoletti Garrett , Galazo Maria , He Fenglei 

TITLE=Deregulated Rac1 Activity in Neural Crest Controls Cell Proliferation, Migration and Differentiation During Midbrain Development

JOURNAL=Frontiers in Cell and Developmental Biology

VOLUME=9

YEAR=2021

URL=https://www.frontiersin.org/journals/cell-and-developmental-biology/articles/10.3389/fcell.2021.704769

DOI=10.3389/fcell.2021.704769

ISSN=2296-634X

ABSTRACT=<p>Mutations in <italic>RAC1</italic> allele are implicated in multiple brain tumors, indicating a rigorous control of Rac1 activity is required for neural tissue normal development and homeostasis. To understand how elevated Rac1 activity affects neural crest cells (NCCs) development, we have generated <italic>Rac1<sup><italic>CA</italic></sup>;Wnt1-Cre2</italic> mice, in which a constitutively active Rac1<sup><italic>G</italic>12<italic>V</italic></sup> mutant is expressed specifically in NCCs derivatives. Our results revealed that augmented Rac1 activity leads to enlarged midbrain and altered cell density, accompanied by increased NCCs proliferation rate and misrouted cell migration. Interestingly, our experimental data also showed that elevated Rac1 activity in NCCs disrupts regionalization of dopaminergic neuron progenitors in the ventral midbrain and impairs their differentiation. These findings shed light on the mechanisms of <italic>RAC1</italic> mutation correlated brain tumor at the cellular and molecular level.</p>