KIF2A regulates the development of dentate granule cells and postnatal hippocampal wiring

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Abstract

Kinesin super family protein 2A (KIF2A), an ATP-dependent microtubule (MT) destabilizer, regulates cell migration, axon elongation, and pruning in the developing nervous system. KIF2A mutations have recently been identified in patients with malformed cortical development. However, postnatal KIF2A is continuously expressed in the hippocampus, in which new neurons are generated throughout an individual's life in established neuronal circuits. In this study, we investigated KIF2A function in the postnatal hippocampus by using tamoxifen-inducible Kif2a conditional knockout (Kif2a-cKO) mice. Despite exhibiting no significant defects in neuronal proliferation or migration, Kif2a-cKO mice showed signs of an epileptic hippocampus. In addition to mossy fiber sprouting, the Kif2a-cKO dentate granule cells (DGCs) showed dendro-axonal conversion, leading to the growth of many aberrant overextended dendrites that eventually developed axonal properties. These results suggested that postnatal KIF2A is a key length regulator of DGC developing neurites and is involved in the establishment of precise postnatal hippocampal wiring.

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Noriko Homma

Department of Cell Biology and Anatomy, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan

Competing interests
The authors declare that no competing interests exist.
Ruyun Zhou

Department of Cell Biology and Anatomy, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan

Competing interests
The authors declare that no competing interests exist.
Muhammad Imran Naseer

Center of Excellence in Genomic Medicine Research, King Abdulaziz University, Jeddah, Saudi Arabia

Competing interests
The authors declare that no competing interests exist.
Adeel G Chaudhary

Center of Excellence in Genomic Medicine Research, King Abdulaziz University, Jeddah, Saudi Arabia

Competing interests
The authors declare that no competing interests exist.
Mohammed H Al-Qahtani

Center of Excellence in Genomic Medicine Research, King Abdulaziz University, Jeddah, Saudi Arabia

Competing interests
The authors declare that no competing interests exist.
Nobutaka Hirokawa

Department of Cell Biology and Anatomy, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan

For correspondence
hirokawa@m.u-tokyo.ac.jp

Competing interests
The authors declare that no competing interests exist.

"This ORCID iD identifies the author of this article:" 0000-0002-0081-5264

Funding

Ministry of Education, Culture, Sports, Science, and Technology (Grant-in-Aid for scientific research)

Nobutaka Hirokawa

King Abdulaziz University (NSTIP strategic technologies program project (12-BIO305059-03))

Nobutaka Hirokawa

King Abdulaziz University (Deanship of Scientific Research (DSR: 1-6-1432/HiCi))

Muhammad Imran Naseer
Adeel G Chaudhary
Mohammed H Al-Qahtani

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.

Ethics

Animal experimentation: This study was performed in strict accordance with the recommendations in the Guide for the Care and Use of Laboratory Animals of the Graduate School of Medicine, University of Tokyo. All of the animals were handled according to approved institutional animal care and use committee protocols of the University of Tokyo. The protocol was approved by the Committee on the Life Science Research Ethics and Safty of the Graduate School of Medicine, University of Tokyo (Permit Number: Med-P10-130-133). All surgery was performed under sodium pentobarbital anesthesia, and every effort was made to minimize suffering.

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This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.