Mad linker phosphorylations control the intensity and range of the BMP-activity gradient in developing Drosophila tissues

Sci Rep. 2014 Nov 7;4:6927. doi: 10.1038/srep06927.

Abstract

The BMP ligand Dpp, operates as a long range morphogen to control many important functions during Drosophila development from tissue patterning to growth. The BMP signal is transduced intracellularly via C-terminal phosphorylation of the BMP transcription factor Mad, which forms an activity gradient in developing embryonic tissues. Here we show that Cyclin dependent kinase 8 and Shaggy phosphorylate three Mad linker serines. We demonstrate that linker phosphorylations control the peak intensity and range of the BMP signal across rapidly developing embryonic tissues. Shaggy knockdown broadened the range of the BMP-activity gradient and increased high threshold target gene expression in the early embryo, while expression of a Mad linker mutant in the wing disc resulted in enhanced levels of C-terminally phosphorylated Mad, a 30% increase in wing tissue, and elevated BMP target genes. In conclusion, our results describe how Mad linker phosphorylations work to control the peak intensity and range of the BMP signal in rapidly developing Drosophila tissues.

Publication types

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

MeSH terms

  • Animals
  • Bone Morphogenetic Proteins / genetics*
  • Bone Morphogenetic Proteins / metabolism
  • Cyclin-Dependent Kinase 8 / genetics
  • Cyclin-Dependent Kinase 8 / metabolism
  • DNA-Binding Proteins / genetics*
  • DNA-Binding Proteins / metabolism
  • Drosophila Proteins / antagonists & inhibitors
  • Drosophila Proteins / genetics*
  • Drosophila Proteins / metabolism
  • Drosophila melanogaster / embryology
  • Drosophila melanogaster / genetics*
  • Drosophila melanogaster / metabolism
  • Embryo, Nonmammalian
  • Gene Expression Regulation, Developmental*
  • Glycogen Synthase Kinase 3 / antagonists & inhibitors
  • Glycogen Synthase Kinase 3 / genetics
  • Glycogen Synthase Kinase 3 / metabolism
  • Morphogenesis / genetics*
  • Phosphorylation
  • RNA, Small Interfering / genetics
  • RNA, Small Interfering / metabolism
  • Signal Transduction
  • Transcription Factors / genetics*
  • Transcription Factors / metabolism
  • Wings, Animal / cytology
  • Wings, Animal / embryology
  • Wings, Animal / metabolism*

Substances

  • Bone Morphogenetic Proteins
  • DNA-Binding Proteins
  • Drosophila Proteins
  • MAD protein, Drosophila
  • RNA, Small Interfering
  • Transcription Factors
  • dpp protein, Drosophila
  • Sgg protein, Drosophila
  • Cyclin-Dependent Kinase 8
  • Glycogen Synthase Kinase 3