JAK/Stat signaling regulates heart precursor diversification in Drosophila

Aaron N. Johnson, Mayssa H. Mokalled, Tom N. Haden, Eric N. Olson

Research output: Contribution to journalArticle

18 Citations (Scopus)

Abstract

Intercellular signal transduction pathways regulate the NK-2 family of transcription factors in a conserved gene regulatory network that directs cardiogenesis in both flies and mammals. The Drosophila NK-2 protein Tinman (Tin) was recently shown to regulate Stat92E, the Janus kinase (JAK) and Signal transducer and activator of transcription (Stat) pathway effector, in the developing mesoderm. To understand whether the JAK/Stat pathway also regulates cardiogenesis, we performed a systematic characterization of JAK/Stat signaling during mesoderm development. Drosophila embryos with mutations in the JAK/Stat ligand upd or in Stat92E have non-functional hearts with luminal defects and inappropriate cell aggregations. Using strong Stat92E lossof- function alleles, we show that the JAK/Stat pathway regulates tin expression prior to heart precursor cell diversification. tin expression can be subdivided into four phases and, in Stat92E mutant embryos, the broad phase 2 expression pattern in the dorsal mesoderm does not restrict to the constrained phase 3 pattern. These embryos also have an expanded pericardial cell domain. We show the E(spl)-C gene HLHm5 is expressed in a pattern complementary to tin during phase 3 and that this expression is JAK/Stat dependent. In addition, E(spl)-C mutant embryos phenocopy the cardiac defects of Stat92E embryos. Mechanistically, JAK/Stat signals activate E(spl)-C genes to restrict Tin expression and the subsequent expression of the T-box transcription factor H15 to direct heart precursor diversification. This study is the first to characterize a role for the JAK/Stat pathway during cardiogenesis and identifies an autoregulatory circuit in which tin limits its own expression domain.

Original languageEnglish (US)
Pages (from-to)4627-4638
Number of pages12
JournalDevelopment
Volume138
Issue number21
DOIs
StatePublished - Nov 1 2011

Fingerprint

Janus Kinases
Transducers
Drosophila
Tin
Embryonic Structures
Mesoderm
Transcription Factors
Cell Aggregation
Gene Regulatory Networks
Diptera
Genes
Mammals
Signal Transduction
Alleles
Ligands
Mutation

Keywords

  • Cardiogenesis
  • Drosophila
  • E(spl)-C
  • JAK/Stat

ASJC Scopus subject areas

  • Developmental Biology
  • Molecular Biology

Cite this

JAK/Stat signaling regulates heart precursor diversification in Drosophila. / Johnson, Aaron N.; Mokalled, Mayssa H.; Haden, Tom N.; Olson, Eric N.

In: Development, Vol. 138, No. 21, 01.11.2011, p. 4627-4638.

Research output: Contribution to journalArticle

Johnson, Aaron N. ; Mokalled, Mayssa H. ; Haden, Tom N. ; Olson, Eric N. / JAK/Stat signaling regulates heart precursor diversification in Drosophila. In: Development. 2011 ; Vol. 138, No. 21. pp. 4627-4638.
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