Akirin is critical for early tinman induction and subsequent formation of the heart in Drosophila melanogaster

Dev Biol. 2021 Jan 1:469:1-11. doi: 10.1016/j.ydbio.2020.09.001. Epub 2020 Sep 17.

Abstract

The regulation of formation of the Drosophila heart by the Nkx 2.5 homologue Tinman is a key event during embryonic development. In this study, we identify the highly conserved transcription cofactor Akirin as a key factor in the earliest induction of tinman by the Twist transcription cofactor. akirin mutant embryos display a variety of morphological defects in the heart, including abnormal spacing between rows of aortic cells and abnormal patterning of the aortic outflow tract. akirin mutant embryos have a greatly reduced level of tinman transcripts, together with a reduction of Tinman protein in the earliest stages of cardiac patterning. Further, akirin mutants have reduced numbers of Tinman-positive cardiomyoblasts, concomitant with disrupted patterning and organization of the heart. Finally, despite the apparent formation of the heart in akirin mutants, these mutant hearts exhibit fewer coordinated contractions in akirin mutants compared with wild-type hearts. These results indicate that Akirin is crucial for the first induction of tinman by the Twist transcription factor, and that the success of the cardiac patterning program is highly dependent upon establishing the proper level of tinman at the earliest steps of the cardiac developmental pathway.

Keywords: Akirin; Cardiac; Drosophila; Embryonic development; Tinman; Twist.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Drosophila Proteins / biosynthesis*
  • Drosophila Proteins / genetics
  • Drosophila Proteins / metabolism
  • Drosophila Proteins / physiology*
  • Drosophila melanogaster / embryology*
  • Drosophila melanogaster / genetics
  • Drosophila melanogaster / metabolism
  • Drosophila melanogaster / physiology
  • Heart / embryology
  • Mutation
  • Myocardial Contraction
  • Myocardium / metabolism
  • Myocardium / pathology
  • Nuclear Proteins / genetics
  • Nuclear Proteins / physiology*
  • RNA, Messenger / metabolism
  • Repressor Proteins / biosynthesis*
  • Repressor Proteins / genetics
  • Trans-Activators / biosynthesis*
  • Trans-Activators / genetics
  • Twist-Related Protein 1 / metabolism

Substances

  • Drosophila Proteins
  • Nuclear Proteins
  • RNA, Messenger
  • Repressor Proteins
  • Trans-Activators
  • Twi protein, Drosophila
  • Twist-Related Protein 1
  • akirin protein, Drosophila
  • tin protein, Drosophila