The TEAD family transcription factor Scalloped regulates blood progenitor maintenance and proliferation in Drosophila through PDGF/VEGFR receptor (Pvr) signaling.
The Drosophila lymph gland is a well-characterized hematopoietic organ in which a population of multipotent stem-like progenitors is maintained by a combination of signals from different cellular populations within the organ. The lymph gland serves as an ideal model both for the interrogation of signaling mechanisms involved in progenitor maintenance as well as a tool for the identification of novel regulatory mechanisms in the highly conserved process of hematopoiesis. Here, we demonstrate a requirement for the TEAD transcription factor Scalloped in the maintenance and proliferation of hematopoietic progenitors. We have characterized a novel population of hemocytes in the early lymph gland identified by the expression of Hand, Scalloped, and the PVR ligand PVF2. In this unique population, we show that Scalloped maintains PVF2 expression, which is required for hemocyte proliferation and achievement of normal lymph gland size. We further demonstrate that STAT signaling marks actively proliferating hemocytes in the early lymph gland, and inhibition of this pathway causes decreased lymph gland growth similar to loss of Scalloped and PVF2, demonstrating a requirement for PVR/STAT signaling in the regulation of lymph gland size. Finally, we demonstrate that Scalloped regulates PVR expression and the maintenance of progenitors downstream of PVR/STAT/ADGF signaling. These findings further establish the role of the TEAD family transcription factors in the regulation of important signaling molecules, and expand our mechanistic insight into the balance between progenitor maintenance and proliferation required for the regulation of lymph gland homeostasis.
Department of Human Genetics, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA 90095, USA.
Gabriel B
GB
Ferguson
Department of Human Genetics, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA 90095, USA; Molecular Biology Institute, Jonsson Comprehensive Cancer Center, UCLA Broad Stem Cell Center, Mattel Children's Hospital UCLA, USA. Electronic address: julianmartinez@mednet.ucla.edu.
Julian A
JA
Martinez-Agosto
D000818:Animals; D030801:Animals, Genetically Modified; D051792:Basic Helix-Loop-Helix Proteins / Q000235:genetics / Q000378:metabolism; D049109:Cell Proliferation / Q000235:genetics*; D029721:Drosophila Proteins / Q000235:genetics* / Q000378:metabolism; D004331:Drosophila melanogaster / Q000235:genetics* / Q000254:growth & development / Q000378:metabolism; D018507:Gene Expression Regulation, Developmental; D006410:Hematopoiesis / Q000235:genetics; D006412:Hematopoietic Stem Cells / Q000378:metabolism*; D006434:Hemocytes / Q000166:cytology / Q000378:metabolism; D006458:Hemolymph / Q000166:cytology / Q000378:metabolism; D007814:Larva / Q000235:genetics / Q000254:growth & development / Q000378:metabolism; D018613:Microscopy, Confocal; D034622:RNA Interference; D020794:Receptor Protein-Tyrosine Kinases / Q000235:genetics* / Q000378:metabolism; D050791:STAT Transcription Factors / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction / Q000235:genetics; D014157:Transcription Factors / Q000235:genetics* / Q000378:metabolism; D042442:Vascular Endothelial Growth Factors / Q000235:genetics / Q000378:metabolism
D051792:Basic Helix-Loop-Helix Proteins; D029721:Drosophila Proteins; D020794:Receptor Protein-Tyrosine Kinases; D050791:STAT Transcription Factors; D014157:Transcription Factors; D042442:Vascular Endothelial Growth Factors; C475488:Hand protein, Drosophila; C528169:Pvf2 protein, Drosophila; C447902:adenosine deaminase-related growth factor, Drosophila; C087984:sd protein, Drosophila; C438368:Pvr protein, Drosophila
Drosophila; Hematopoiesis; Lymph gland; PVF2; PVR; Scalloped