Mad linker phosphorylations control the intensity and range of the BMP-activity gradient in developing Drosophila tissues.
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.
Department of Biological Sciences, California State University Los Angeles, 5151 State University Dr., Los Angeles, CA 90032, USA.
Abigail
A
Aleman
Department of Biological Sciences, California State University Los Angeles, 5151 State University Dr., Los Angeles, CA 90032, USA.
Marlyn
M
Rios
Department of Biological Sciences, California State University Los Angeles, 5151 State University Dr., Los Angeles, CA 90032, USA.
Matthew
M
Juarez
Department of Biological Sciences, California State University Los Angeles, 5151 State University Dr., Los Angeles, CA 90032, USA.
Daniel
D
Lee
Department of Biological Sciences, California State University Los Angeles, 5151 State University Dr., Los Angeles, CA 90032, USA.
Annan
A
Chen
Department of Biological Sciences, California State University Los Angeles, 5151 State University Dr., Los Angeles, CA 90032, USA.
Edward
E
Eivers
D000818:Animals; D019485:Bone Morphogenetic Proteins / Q000235:genetics* / Q000378:metabolism; D056850:Cyclin-Dependent Kinase 8 / Q000235:genetics / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000235:genetics* / Q000378:metabolism; D029721:Drosophila Proteins / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000378:metabolism; D004331:Drosophila melanogaster / Q000196:embryology / Q000235:genetics* / Q000378:metabolism; D004625:Embryo, Nonmammalian; D018507:Gene Expression Regulation, Developmental; D038362:Glycogen Synthase Kinase 3 / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D009024:Morphogenesis / Q000235:genetics*; D010766:Phosphorylation; D034741:RNA, Small Interfering / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction; D014157:Transcription Factors / Q000235:genetics* / Q000378:metabolism; D014921:Wings, Animal / Q000166:cytology / Q000196:embryology / Q000378:metabolism*
D019485:Bone Morphogenetic Proteins; D004268:DNA-Binding Proteins; D029721:Drosophila Proteins; C112506:MAD protein, Drosophila; D034741:RNA, Small Interfering; D014157:Transcription Factors; C064196:dpp protein, Drosophila; C080335:Sgg protein, Drosophila; D056850:Cyclin-Dependent Kinase 8; D038362:Glycogen Synthase Kinase 3