PUBLICATION
Modeling of large-scale hoxbb cluster deletions in zebrafish uncovers a role for segmentation pathways in atrioventricular boundary specification
- Authors
- Hu, P., Wang, B., Jin, D., Gu, Y., He, H., Meng, X., Zhu, W., Chiang, D.Y., Li, W., MacRae, C.A., Zu, Y.
- ID
- ZDB-PUB-231007-56
- Date
- 2023
- Source
- Cellular and molecular life sciences : CMLS 80: 317317 (Journal)
- Registered Authors
- MacRae, Calum A.
- Keywords
- CRISPR, Heart development, Zebrafish, hoxb1b, hoxbb cluster
- MeSH Terms
-
- Animals
- Gene Expression Regulation, Developmental
- Heart
- Humans
- Transcription Factors/metabolism
- Zebrafish*/genetics
- Zebrafish*/metabolism
- Zebrafish Proteins*/genetics
- Zebrafish Proteins*/metabolism
- PubMed
- 37801106 Full text @ Cell. Mol. Life Sci.
Citation
Hu, P., Wang, B., Jin, D., Gu, Y., He, H., Meng, X., Zhu, W., Chiang, D.Y., Li, W., MacRae, C.A., Zu, Y. (2023) Modeling of large-scale hoxbb cluster deletions in zebrafish uncovers a role for segmentation pathways in atrioventricular boundary specification. Cellular and molecular life sciences : CMLS. 80:317317.
Abstract
Hox genes orchestrate the segmental specification of the muscular circulatory system in invertebrates but it has not proven straightforward to decipher segmental parallels in the vertebrate heart. Recently, patients with HOXB gene cluster deletion were found to exhibit abnormalities including atrioventricular canal defects. Using CRISPR, we established a mutant with the orthologous hoxbb cluster deletion in zebrafish. The mutant exhibited heart failure and atrioventricular regurgitation at 5 days. Analyzing the four genes in the hoxbb cluster, isolated deletion of hoxb1b-/- recapitulated the cardiac abnormalities, supporting hoxb1b as the causal gene. Both in situ and in vitro data indicated that hoxb1b regulates gata5 to inhibit hand2 expression and ultimately is required to pattern the vertebrate atrioventricular boundary. Together, these data reveal a role for segmental specification in vertebrate cardiac development and highlight the utility of CRISPR techniques for efficiently exploring the function of large structural genomic lesions.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping