Genetic compensation by epobin pronephros development in epoamutant zebrafish

Autor: She, Jianqing, Wu, Yue, Lou, Bowen, Lodd, Elisabeth, Klems, Alina, Schmoehl, Felix, Yuan, Zuyi, Noble, Ferdinand Le, Kroll, Jens
Zdroj: Cell Cycle; October 2019, Vol. 18 Issue: 20 p2683-2696, 14p
Abstrakt: ABSTRACTZebrafish erythropoietin a (epoa) is a well characterized regulator of red blood cell formation. Recent morpholino mediated knockdown data have also identified epoabeing essential for physiological pronephros development in zebrafish, which is driven by blocking apoptosis in developing kidneys. Yet, zebrafish mutants for epoahave not been described so far. In order to compare a transient knockdown vs. permanent knockout for epoain zebrafish on pronephros development, we used CRISPR/Cas9 technology to generate epoaknockout zebrafish mutants and we performed structural and functional studies on pronephros development. In contrast to epoamorphants, epoa−/-zebrafish mutants showed normal pronephros structure; however, a previously uncharacterized gene in zebrafish, named epob, was identified and upregulated in epoa−/-mutants. epobknockdown altered pronephros development, which was further aggravated in epoa−/-mutants. Likewise, epoaand epobmorphants regulated similar and differential gene signatures related to kidney development in zebrafish. In conclusion, stable loss of epoaduring embryonic development can be compensated by epobleading to phenotypical discrepancies in epoaknockdown and knockout zebrafish embryos.
Databáze: Supplemental Index