Abstract
Perturbation of CaMKIIβ expression has been associated with multiple neuropsychiatric diseases, highlighting CaMKIIβ as a gene of interest. Yet, in contrast to CaMKIIα, the specific functions of CaMKIIβ in the brain remain poorly explored. Here, we reveal a novel function for this CaMKII isoform in vivo during neuronal development. By using in utero electroporation, we show that CaMKIIβ is an important regulator of radial migration of projection neurons during cerebral cortex development. Knockdown of CaMKIIβ causes accelerated migration of nascent pyramidal neurons, whereas overexpression of CaMKIIβ inhibits migration, demonstrating that precise regulation of CaMKIIβ expression is required for correct neuronal migration. More precisely, CaMKIIβ controls the multipolar-bipolar transition in the intermediate zone and locomotion in the cortical plate through its actin-binding and -bundling activities. In addition, our data indicate that a fine-tuned balance between CaMKIIβ and cofilin activities is necessary to ensure proper migration of cortical neurons. Thus, our findings define a novel isoform-specific function for CaMKIIβ, demonstrating that CaMKIIβ has a major biological function in the developing brain.
Highlights
During brain development, neurons migrate extensively after their birth to reach their final destination, where they establish connections with other neurons and contribute to circuit formation
CaMKIIβ cloned into the pEGFP-C1 vector was a kind gift from Dr Paul De Koninck, CaMKIIβ-ΔFABD, CaMKIIβ-Δasso, CaMKIIβ-K43R and CaMKIIβΔCTS cloned into the pEGFP-C1 vector from Dr Azad Bonni, CaMKIIβ-All A and CaMKIIβ-All D cloned into the pEGFP-C1 vector from Dr Yasunori Hayashi, pcDNAcofilinS3D, pcDNA-cofilinS3A and pcDNA-cofilinWT from Iryna M
We first showed by real-time PCR that CaMKIIβ expression increases significantly between E12.5 and postnatal day 0 (P0) (Figure 1a and Supplementary Figure 1b) whereas CaMKIIα transcripts are poorly expressed until birth (Supplementary Figure 1a)
Summary
Neurons migrate extensively after their birth to reach their final destination, where they establish connections with other neurons and contribute to circuit formation. Upon multi to bipolar transition, neurons establish dynamic contacts with radial glia fibers and subsequently use them as a scaffold to migrate to the upper part of the CP using a mode of migration called locomotion 6. This movement is characterized by repetitive cycles of synchronized steps - formation of a cytoplasmic dilatation in the proximal region of the leading process, movement of the centrosome towards the swelling and translocation of the nucleus towards the centrosome - conferring a saltatory advancement to locomoting neurons [7, 8]. Once neurons approach their final location, they change again their mode of migration from locomotion to terminal translocation and settle in a specific cortical layer 9
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
