PUBLICATION
Ankle2 deficiency-associated microcephaly and spermatogenesis defects in zebrafish are alleviated by heterozygous deletion of vrk1
- Authors
- Apridita Sebastian, W., Shiraishi, H., Shimizu, N., Umeda, R., Lai, S., Ikeuchi, M., Morisaki, I., Yano, S., Yoshimura, A., Hanada, R., Hanada, T.
- ID
- ZDB-PUB-220809-14
- Date
- 2022
- Source
- Biochemical and Biophysical Research Communications 624: 95-101 (Journal)
- Registered Authors
- Hanada, Reiko, Hanada, Toshikatsu, Shimizu, Nobuyuki
- Keywords
- Ankle2, MCPH, Microcephaly, Vrk1, Zebrafish
- MeSH Terms
-
- Protein Serine-Threonine Kinases
- Intracellular Signaling Peptides and Proteins
- Zika Virus Infection*
- Zika Virus*
- Mutation
- Animals
- Male
- Spermatogenesis
- Microcephaly*/genetics
- Microcephaly*/pathology
- Zebrafish/genetics
- Zebrafish/metabolism
- PubMed
- 35940133 Full text @ Biochem. Biophys. Res. Commun.
Citation
Apridita Sebastian, W., Shiraishi, H., Shimizu, N., Umeda, R., Lai, S., Ikeuchi, M., Morisaki, I., Yano, S., Yoshimura, A., Hanada, R., Hanada, T. (2022) Ankle2 deficiency-associated microcephaly and spermatogenesis defects in zebrafish are alleviated by heterozygous deletion of vrk1. Biochemical and Biophysical Research Communications. 624:95-101.
Abstract
Autosomal recessive primary microcephaly (MCPH) is a rare congenital disorder characterized by a below average brain volume at birth and is associated with neurodevelopmental disorders such as growth retardation and intellectual disability. Mutations in ANKLE2 have been identified as one of the causes of MCPH (MCPH16). ANKLE2 is a target molecule of the Zika virus NS4a protein that interferes with ANKLE2 function, resulting in severe microcephaly. ANKLE2 is essential for organizing the nuclear envelope and chromatin structures during the mitotic-end process via barrier to autointegration factor (BAF) dephosphorylation. However, the precise mechanism by which the loss of ANKLE2 function causes the pathogenesis of microcephaly remains unclear. In this study, we generated Ankle2-deficient zebrafish (ankle2-/-) with a significant reduction in brain size compared with that of their control siblings. The ankle2-/- brain showed a significant decrease in the number of radial glial progenitor cells, suggesting that Ankle2 deficiency in zebrafish causes neurogenesis defects. Furthermore, ankle2-/- male zebrafish showed infertility owing to defects in spermatogenesis. Notably, microcephaly was overcome by vrk1 morpholino knockdown or vrk1 heterozygous deletion. In addition, spermatogenesis in ankle2-/- zebrafish males was partially restored by the vrk1 heterozygous deletion, although infertility was not resolved. These results indicate that ANKLE2 and VRK1 coordinate with each other for BAF phosphorylation to maintain normal mitosis during neurogenesis and spermatogenesis.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping