Zfh1 promotes survival of a peripheral glia subtype by antagonizing a Jun N-terminal kinase-dependent apoptotic pathway.
In Drosophila subperineurial glia (SPG) ensheath and insulate the nerve. SPG is under strict cell cycle and survival control because cell division or death of such a cell type would compromise the integrity of the blood-nerve barrier. The mechanisms underlying the survival of SPG remain unknown. Here, we show that the embryonic peripheral glia expresses the Zfh1 transcription factor, and in zfh1 mutants a particular SPG subtype, ePG10, undergoes apoptosis. Our findings show that in ePG10, Zfh1 represses the pro-apoptotic RHG-motif gene reaper in a cell-autonomous manner. Zfh1 also blocks the activation of the Jun N-terminal kinase (JNK) pathway, and reducing or enhancing JNK signalling in zfh1 mutants prevents or promotes ePG10 apoptosis. Our study shows a novel function for Zfh1 as an anti-apoptotic molecule and uncovers a cryptic JNK-dependent apoptotic programme in ePG10, which is normally blocked by Zfh1. We propose that, in cells such as SPG that do not undergo self-renewal and survive long periods, transcriptional control of RHG-motif gene expression together with fine tuning of JNK signalling is crucial for cell survival.
Ohayon
David
D
INSERM U583, INM-Hopital St Eloi, 80 rue Augustin Fliche, Montpellier Cedex, France.
Pattyn
Alexandre
A
Venteo
Stephanie
S
Valmier
Jean
J
Carroll
Patrick
P
Garces
Alain
A
D000818:Animals; D017209:Apoptosis / Q000235:genetics / Q000502:physiology*; D015153:Blotting, Western; D002454:Cell Differentiation / Q000235:genetics / Q000502:physiology; D029721:Drosophila Proteins / Q000235:genetics / Q000502:physiology*; D004331:Drosophila melanogaster / Q000201:enzymology / Q000378:metabolism / Q000502:physiology*; D051034:Inhibitor of Apoptosis Proteins / Q000235:genetics / Q000502:physiology; D048031:JNK Mitogen-Activated Protein Kinases / Q000235:genetics / Q000502:physiology*; D009457:Neuroglia / Q000166:cytology* / Q000378:metabolism*; D017933:Peripheral Nervous System / Q000378:metabolism; D012097:Repressor Proteins / Q000235:genetics / Q000502:physiology*; D015398:Signal Transduction / Q000235:genetics / Q000502:physiology
C111891:DIAP1 protein, Drosophila; D029721:Drosophila Proteins; D051034:Inhibitor of Apoptosis Proteins; D012097:Repressor Proteins; C081010:zfh1 protein, Drosophila; D048031:JNK Mitogen-Activated Protein Kinases