Phosphorylated Groucho delays differentiation in the follicle stem cell lineage by providing a molecular memory of EGFR signaling in the niche.
In the epithelial follicle stem cells (FSCs) of the Drosophila ovary, Epidermal Growth Factor Receptor (EGFR) signaling promotes self-renewal, whereas Notch signaling promotes differentiation of the prefollicle cell (pFC) daughters. We have identified two proteins, Six4 and Groucho (Gro), that link the activity of these two pathways to regulate the earliest cell fate decision in the FSC lineage. Our data indicate that Six4 and Gro promote differentiation towards the polar cell fate by promoting Notch pathway activity. This activity of Gro is antagonized by EGFR signaling, which inhibits Gro-dependent repression via p-ERK mediated phosphorylation. We have found that the phosphorylated form of Gro persists in newly formed pFCs, which may delay differentiation and provide these cells with a temporary memory of the EGFR signal. Collectively, these findings demonstrate that phosphorylated Gro labels a transition state in the FSC lineage and describe the interplay between Notch and EGFR signaling that governs the differentiation processes during this period.
The University of California, San Francisco, Departments of Anatomy and OB-GYN/RS, CA 94122, USA.
Michael J
MJ
Johnston
The Hebrew University, Department of Developmental Biology and Cancer Research, IMRIC, Faculty of Medicine, Jerusalem 9112102, Israel.
Shaked
S
Bar-Cohen
The Hebrew University, Department of Developmental Biology and Cancer Research, IMRIC, Faculty of Medicine, Jerusalem 9112102, Israel.
Ze'ev
Z
Paroush
The University of California, San Francisco, Departments of Anatomy and OB-GYN/RS, CA 94122, USA todd.nystul@ucsf.edu.
Todd G
0000-0002-6250-2394
TG
Nystul
D000818:Animals; D051792:Basic Helix-Loop-Helix Proteins / Q000235:genetics*; D002454:Cell Differentiation / Q000235:genetics; D029721:Drosophila Proteins / Q000235:genetics* / Q000378:metabolism*; D004331:Drosophila melanogaster / Q000196:embryology*; D004847:Epithelial Cells / Q000166:cytology; D066246:ErbB Receptors / Q000378:metabolism*; D005260:Female; D018398:Homeodomain Proteins / Q000235:genetics* / Q000378:metabolism; D009419:Nerve Tissue Proteins / Q000235:genetics* / Q000378:metabolism; D006080:Ovarian Follicle / Q000166:cytology / Q000196:embryology*; D010766:Phosphorylation; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000235:genetics; D018010:Receptors, Invertebrate Peptide / Q000378:metabolism*; D051880:Receptors, Notch / Q000378:metabolism*; D012097:Repressor Proteins / Q000235:genetics*; D015398:Signal Transduction / Q000235:genetics; D013234:Stem Cells / Q000166:cytology; D014157:Transcription Factors / Q000235:genetics* / Q000378:metabolism
D051792:Basic Helix-Loop-Helix Proteins; D029721:Drosophila Proteins; D066246:ErbB Receptors; D018398:Homeodomain Proteins; D009419:Nerve Tissue Proteins; D034741:RNA, Small Interfering; D018010:Receptors, Invertebrate Peptide; D051880:Receptors, Notch; D012097:Repressor Proteins; D014157:Transcription Factors; C497759:N protein, Drosophila; C434485:Six4 protein, Drosophila; C091023:gro protein, Drosophila; C066532:Egfr protein, Drosophila
Drosophila; EGFR; Epithelial stem cell; Groucho; Ovary; Six4