PUBLICATION
MEF2C contributes to axonal branching by regulating Kif2c transcription
- Authors
- Wu, R., Sun, Y., Zhou, Z., Dong, Z., Liu, Y., Liu, M., Gao, H.
- ID
- ZDB-PUB-240426-14
- Date
- 2024
- Source
- The European journal of neuroscience 59(12): 3389-3402 (Journal)
- Registered Authors
- Dong, Zhangji
- Keywords
- KIF2C, MEF2C, axonal branching, neurons, zebrafish
- MeSH Terms
-
- Animals
- Zebrafish*
- Humans
- Gene Expression Regulation, Developmental
- Zebrafish Proteins/genetics
- Zebrafish Proteins/metabolism
- Axons*/metabolism
- Axons*/physiology
- Kinesins*/genetics
- Kinesins*/metabolism
- MEF2 Transcription Factors*/genetics
- MEF2 Transcription Factors*/metabolism
- Motor Neurons/metabolism
- Neurogenesis/physiology
- PubMed
- 38663879 Full text @ Eur. J. Neurosci.
Citation
Wu, R., Sun, Y., Zhou, Z., Dong, Z., Liu, Y., Liu, M., Gao, H. (2024) MEF2C contributes to axonal branching by regulating Kif2c transcription. The European journal of neuroscience. 59(12):3389-3402.
Abstract
Neurons are post-mitotic cells, with microtubules playing crucial roles in axonal transport and growth. Kinesin family member 2c (KIF2C), a member of the Kinesin-13 family, possesses the ability to depolymerize microtubules and is involved in remodelling the microtubule lattice. Myocyte enhancer factor 2c (MEF2C) was initially identified as a regulator of muscle differentiation but has recently been associated with neurological abnormalities such as severe cognitive impairment, stereotyping, epilepsy and brain malformations when mutated or deleted. However, further investigation is required to determine which target genes MEF2C acts upon to influence neuronal function as a transcription regulator. Our data demonstrate that knockdown of both Mef2c and Kif2c significantly impacts spinal motor neuron development and behaviour in zebrafish. Luciferase reporter assays and chromosome immunoprecipitation assays, along with down/upregulated expression analysis, revealed that MFE2C functions as a novel transcription regulator for the Kif2c gene. Additionally, the knockdown of either Mef2c or Kif2c expression in E18 cortical neurons substantially reduces the number of primary neurites and axonal branches during neuronal development in vitro without affecting neurite length. Finally, depletion of Kif2c eliminated the effects of overexpression of Mef2c on the neurite branching. Based on these findings, we provided novel evidence demonstrating that MEF2C regulates the transcription of the Kif2c gene thereby influencing the axonal branching.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping