TY - JOUR
T1 - Insulin signaling acts in adult adipocytes via GSK-3β and independently of FOXO to control Drosophila female germline stem cell numbers
AU - Armstrong, Alissa R.
AU - Drummond-Barbosa, Daniela
N1 - Funding Information:
A.R.A. and D.D.-B. designed the experiments and wrote the manuscript. A.R.A. performed the experiments. A.R.A. and D.D.-B. interpreted the experiments. We thank B. Cauwalder, P. Leopold, E. Matunis, the Bloomington Stock Center, the Vienna Drosophila RNAi Center, the TRiP at Harvard Medical School, and the Developmental Studies Hybridoma Bank for fly stocks and reagents. We thank members of the Drummond-Barbosa laboratory for helpful discussion and comments on this manuscript. This work was supported by National Institutes of Health R01 GM 069875 (D.D.-B.). A.R.A. was supported by training Grant T32 CA 009110 and National Research Service Award F32 GM 106718 from the National Institutes of Health.
Funding Information:
A.R.A. and D.D.-B. designed the experiments and wrote the manuscript. A.R.A. performed the experiments. A.R.A. and D.D.-B. interpreted the experiments. We thank B. Cauwalder, P. Leopold, E. Matunis, the Bloomington Stock Center, the Vienna Drosophila RNAi Center, the TRiP at Harvard Medical School, and the Developmental Studies Hybridoma Bank for fly stocks and reagents. We thank members of the Drummond-Barbosa laboratory for helpful discussion and comments on this manuscript. This work was supported by National Institutes of Health R01 GM 069875 (D.D.-B.). A.R.A. was supported by training Grant T32 CA 009110 and National Research Service Award F32 GM 106718 from the National Institutes of Health .
Publisher Copyright:
© 2018 Elsevier Inc.
PY - 2018/8/1
Y1 - 2018/8/1
N2 - Tissue-specific stem cells are tied to the nutritional and physiological environment of adult organisms. Adipocytes have key endocrine and nutrient-sensing roles and have emerged as major players in relaying dietary information to regulate other organs. For example, previous studies in Drosophila melanogaster revealed that amino acid sensing as well as diet-dependent metabolic pathways function in adipocytes to influence the maintenance of female germline stem cells (GSCs). How nutrient-sensing pathways acting within adipocytes influence adult stem cell lineages, however, is just beginning to be elucidated. Here, we report that insulin/insulin-like growth factor signaling in adipocytes promotes GSC maintenance, early germline cyst survival, and vitellogenesis. Further, adipocytes use distinct mechanisms downstream of insulin receptor activation to control these aspects of oogenesis, all of which are independent of FOXO. We find that GSC maintenance is modulated by Akt1 through GSK-3β early germline cyst survival is downstream of adipocyte Akt1 but independent of GSK-3β and vitellogenesis is regulated through an Akt1-independent pathway in adipocytes. These results indicate that, in addition to employing different types of nutrient sensing, adipocytes can use distinct axes of a single nutrient-sensing pathway to regulate multiple stages of the GSC lineage in the ovary.
AB - Tissue-specific stem cells are tied to the nutritional and physiological environment of adult organisms. Adipocytes have key endocrine and nutrient-sensing roles and have emerged as major players in relaying dietary information to regulate other organs. For example, previous studies in Drosophila melanogaster revealed that amino acid sensing as well as diet-dependent metabolic pathways function in adipocytes to influence the maintenance of female germline stem cells (GSCs). How nutrient-sensing pathways acting within adipocytes influence adult stem cell lineages, however, is just beginning to be elucidated. Here, we report that insulin/insulin-like growth factor signaling in adipocytes promotes GSC maintenance, early germline cyst survival, and vitellogenesis. Further, adipocytes use distinct mechanisms downstream of insulin receptor activation to control these aspects of oogenesis, all of which are independent of FOXO. We find that GSC maintenance is modulated by Akt1 through GSK-3β early germline cyst survival is downstream of adipocyte Akt1 but independent of GSK-3β and vitellogenesis is regulated through an Akt1-independent pathway in adipocytes. These results indicate that, in addition to employing different types of nutrient sensing, adipocytes can use distinct axes of a single nutrient-sensing pathway to regulate multiple stages of the GSC lineage in the ovary.
KW - Adipocytes
KW - Drosophila
KW - GSK-3β
KW - Germline stem cells
KW - Insulin signaling
KW - Oogenesis
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U2 - 10.1016/j.ydbio.2018.04.028
DO - 10.1016/j.ydbio.2018.04.028
M3 - Article
C2 - 29729259
AN - SCOPUS:85046636254
SN - 0012-1606
VL - 440
SP - 31
EP - 39
JO - Developmental biology
JF - Developmental biology
IS - 1
ER -