Zebrafish Paralogs brd2a and brd2b Are Needed for Proper Circulatory, Excretory and Central Nervous System Formation and Act as Genetic Antagonists during Development

Authors

Gregory L Branigan, University of Arizona College of Medicine-Tucson
Kelly S Olsen, University of North Carolina School of Medicine-Chapel Hill
Isabella Burda, Cornell University
Matthew W Haemmerle, University of Pennsylvania
Jason Ho, Rutgers University
Alexandra Venuto, East Carolina University
Nicholas D D'Antonio, Thomas Jefferson UniversityFollow
Ian E Briggs, Villanova University
Angela J DiBenedetto, Villanova University

Document Type

Article

Publication Date

10-31-2021

Comments

This article is the author’s final published version in Journal of Developmental Biology, Volume 9, Issue 4, October 2021, Article number 46.

The published version is available at https://doi.org/10.3390/jdb9040046. Copyright © Branigan et al.

Abstract

Brd2 belongs to the BET family of epigenetic transcriptional co-regulators that act as adaptor-scaffolds for the assembly of chromatin-modifying complexes and other factors at target gene promoters. Brd2 is a protooncogene and candidate gene for juvenile myoclonic epilepsy in humans, a homeobox gene regulator in Drosophila, and a maternal-zygotic factor and cell death modulator that is necessary for normal development of the vertebrate central nervous system (CNS). As two copies of Brd2 exist in zebrafish, we use antisense morpholino knockdown to probe the role of paralog Brd2b, as a comparative study to Brd2a, the ortholog of human Brd2. A deficiency in either paralog results in excess cell death and dysmorphology of the CNS, whereas only Brd2b deficiency leads to loss of circulation and occlusion of the pronephric duct. Co-knockdown of both paralogs suppresses single morphant defects, while co-injection of morpholinos with paralogous RNA enhances them, suggesting novel genetic interaction with functional antagonism. Brd2 diversification includes paralog-specific RNA variants, a distinct localization of maternal factors, and shared and unique spatiotemporal expression, providing unique insight into the evolution and potential functions of this gene.

Recommended Citation

Branigan, Gregory L; Olsen, Kelly S; Burda, Isabella; Haemmerle, Matthew W; Ho, Jason; Venuto, Alexandra; D'Antonio, Nicholas D; Briggs, Ian E; and DiBenedetto, Angela J, "Zebrafish Paralogs brd2a and brd2b Are Needed for Proper Circulatory, Excretory and Central Nervous System Formation and Act as Genetic Antagonists during Development" (2021). Department of Biochemistry and Molecular Biology Faculty Papers. Paper 198.
https://jdc.jefferson.edu/bmpfp/198

Creative Commons License

This work is licensed under a Creative Commons Attribution 4.0 License.

PubMed ID

34842711

Language

English