The Celsr3-Kif2a axis directs neuronal migration in the postnatal brain

Inhibitory synapse dysfunction and epileptic susceptibility associated with KIF2A deletion in cortical interneurons

“…During embryonic development, KIF2A is ubiquitously expressed in the forebrain ( Figure 1A ). We inactivated the Kif2a gene in GABAergic neurons by crossing the Dlx5/6-Cre-IRES-eGFP line with Kif2a F/F mice ( Stenman et al, 2003 ; Hakanen et al, 2021 ). We used the eGFP transgene to monitor expression of Dlx5/6 promoter, and KIFA2 immunofluorescence to monitor recombination ( Figure 1A ).…”

“…The day of vaginal plug was considered as embryonic day 0.5 (E0.5). We used the following mouse lines: Kif2a F/F ( Hakanen et al, 2021 ) and Dlx5/6Cre-eGFP ( Stenman et al, 2003 ). To produce Kif2a FlF ; Dlx5/6Cre-eGFP (referred to as Dlx5/6-Kif2a cKO ), we crossed Dlx5/6Cre-eGFP ; Kif2a F/+ males with Kif2a F/+ females.…”

“…Specific deletion of KIF2A in pallial glutamatergic neurons during development leads to laminar disorganization in the cortex, abnormal neuronal morphology and connectivity and premature neurodegeneration ( Ruiz-Reig et al, 2022 ). KIF2A is also required for adult neurogenesis and tangential migration of neuroblasts in the rostral migratory stream toward olfactory bulbs ( Hakanen et al, 2021 ).…”

WNT signaling at the intersection between neurogenesis and brain tumorigenesis

“…Like in embryonic neurogenesis, WNT signaling is essential for adult neurogenesis ( Lie et al, 2005 ; Kuwabara et al, 2009 ; Munji et al, 2011 ). WNT molecules are involved in numerous steps of adult neurogenesis, including self-renewal, activation of quiescent NSCs, proliferation, differentiation, maturation, and functional integration of newly formed neurons ( Lake and Sokol, 2009 ; Ezan et al, 2021 ; Hakanen et al, 2022 ). Mutations in WNT genes affect the proliferation and differentiation of NSCs ( Xu et al, 2020 ).…”

“…The WNT/PCP genes also have a crucial role in connectivity by regulating neuronal migration, axon guidance, and dendritic morphogenesis ( Tissir and Goffinet, 2013 ; Boutin et al, 2014 ; Goffinet and Tissir, 2017 ). The core components of WNT/PCP regulate the directionality and extent of tangential migration of neurons in the embryonic and postnatal brains ( Vivancos et al, 2009 ; Wada and Okamoto, 2009 ; Qu et al, 2010b ; Sittaramane et al, 2013 ; Glasco et al, 2016 ; Hakanen et al, 2022 ). CELSR1-3 and FZD3 are expressed in nascent neurons and govern their axon navigation.…”