The defender against apoptotic cell death 1 gene is required for tissue growth and efficient N-glycosylation in Drosophila melanogaster.
How organ growth is regulated in multicellular organisms is a long-standing question in developmental biology. It is known that coordination of cell apoptosis and proliferation is critical in cell number and overall organ size control, while how these processes are regulated is still under investigation. In this study, we found that functional loss of a gene in Drosophila, named Drosophila defender against apoptotic cell death 1 (dDad1), leads to a reduction of tissue growth due to increased apoptosis and lack of cell proliferation. The dDad1 protein, an orthologue of mammalian Dad1, was found to be crucial for protein N-glycosylation in developing tissues. Our study demonstrated that loss of dDad1 function activates JNK signaling and blocking the JNK pathway in dDad1 knock-down tissues suppresses cell apoptosis and partially restores organ size. In addition, reduction of dDad1 triggers ER stress and activates unfolded protein response (UPR) signaling, prior to the activation of JNK signaling. Furthermore, Perk-Atf4 signaling, one branch of UPR pathways, appears to play a dual role in inducing cell apoptosis and mediating compensatory cell proliferation in this dDad1 knock-down model.
Intercollege Graduate Degree Program in Genetics, The Pennsylvania State University, University Park, PA, United States.
Yifan
Y
Zhang
Department of Biochemistry and Molecular Biology, The Pennsylvania State University, University Park, PA, United States.
Chang
C
Cui
Intercollege Graduate Degree Program in Genetics, The Pennsylvania State University, University Park, PA, United States; Department of Biochemistry and Molecular Biology, The Pennsylvania State University, University Park, PA, United States; Department of Biology, The Pennsylvania State University, University Park, PA, United States. Electronic address: zcl1@psu.edu.
Zhi-Chun
ZC
Lai
D000818:Animals; D017209:Apoptosis / Q000235:genetics; D055162:Biocatalysis; D049109:Cell Proliferation; D002999:Clone Cells; D029721:Drosophila Proteins / Q000235:genetics* / Q000378:metabolism; D004331:Drosophila melanogaster / Q000166:cytology / Q000235:genetics* / Q000254:growth & development* / Q000378:metabolism; D004721:Endoplasmic Reticulum / Q000378:metabolism; D059865:Endoplasmic Reticulum Stress; D055785:Gene Knockdown Techniques; D017344:Genes, Insect; D006031:Glycosylation; D048031:JNK Mitogen-Activated Protein Kinases / Q000378:metabolism; D020935:MAP Kinase Signaling System; D008954:Models, Biological; D009024:Morphogenesis / Q000235:genetics*; D009154:Mutation / Q000235:genetics; D021122:Protein Subunits / Q000378:metabolism; D013347:Subcellular Fractions / Q000378:metabolism
D029721:Drosophila Proteins; D021122:Protein Subunits; D048031:JNK Mitogen-Activated Protein Kinases