TY - JOUR
T1 - Insulin signals control the competence of the Drosophila female germline stem cell niche to respond to Notch ligands
AU - Hsu, Hwei Jan
AU - Drummond-Barbosa, Daniela
N1 - Funding Information:
We thank E. Hafen, L. Dobens, G. Fishcher, A. Spradling, P. Lasko, E. Knust, K. Irvine, U. Banerjee, J. Axelrod, the Bloomington Stock Center, and the Developmental Studies Hybridoma Bank for Drosophila stocks and antibodies. We also thank E. Ables and L. LaFever for valuable comments on this article. This work was supported by American Cancer Society Grant RSG-07-182-01-DDC .
PY - 2011/2/15
Y1 - 2011/2/15
N2 - Adult stem cells reside in specialized microenvironments, or niches, that are essential for their function in vivo. Stem cells are physically attached to the niche, which provides secreted factors that promote their self-renewal and proliferation. Despite intense research on the role of the niche in regulating stem cell function, much less is known about how the niche itself is controlled. We previously showed that insulin signals directly stimulate germline stem cell (GSC) division and indirectly promote GSC maintenance via the niche in Drosophila. Insulin-like peptides are required for maintenance of cap cells (a major component of the niche) via modulation of Notch signaling, and they also control attachment of GSCs to cap cells and E-cadherin levels at the cap cell-GSC junction. Here, we further dissect the molecular and cellular mechanisms underlying these processes. We show that insulin and Notch ligands directly stimulate cap cells to maintain their numbers and indirectly promote GSC maintenance. We also report that insulin signaling, via phosphoinositide 3-kinase and FOXO, intrinsically controls the competence of cap cells to respond to Notch ligands and thereby be maintained. Contrary to a previous report, we also find that Notch ligands originated in GSCs are not required either for Notch activation in the GSC niche, or for cap cell or GSC maintenance. Instead, the niche itself produces ligands that activate Notch signaling within cap cells, promoting stability of the GSC niche. Finally, insulin signals control cap cell-GSC attachment independently of their role in Notch signaling. These results are potentially relevant to many systems in which Notch signaling modulates stem cells and demonstrate that complex interactions between local and systemic signals are required for proper stem cell niche function.
AB - Adult stem cells reside in specialized microenvironments, or niches, that are essential for their function in vivo. Stem cells are physically attached to the niche, which provides secreted factors that promote their self-renewal and proliferation. Despite intense research on the role of the niche in regulating stem cell function, much less is known about how the niche itself is controlled. We previously showed that insulin signals directly stimulate germline stem cell (GSC) division and indirectly promote GSC maintenance via the niche in Drosophila. Insulin-like peptides are required for maintenance of cap cells (a major component of the niche) via modulation of Notch signaling, and they also control attachment of GSCs to cap cells and E-cadherin levels at the cap cell-GSC junction. Here, we further dissect the molecular and cellular mechanisms underlying these processes. We show that insulin and Notch ligands directly stimulate cap cells to maintain their numbers and indirectly promote GSC maintenance. We also report that insulin signaling, via phosphoinositide 3-kinase and FOXO, intrinsically controls the competence of cap cells to respond to Notch ligands and thereby be maintained. Contrary to a previous report, we also find that Notch ligands originated in GSCs are not required either for Notch activation in the GSC niche, or for cap cell or GSC maintenance. Instead, the niche itself produces ligands that activate Notch signaling within cap cells, promoting stability of the GSC niche. Finally, insulin signals control cap cell-GSC attachment independently of their role in Notch signaling. These results are potentially relevant to many systems in which Notch signaling modulates stem cells and demonstrate that complex interactions between local and systemic signals are required for proper stem cell niche function.
KW - Cap cell
KW - Drosophila
KW - Germline stem cell
KW - Insulin
KW - Neuralized
KW - Notch
UR - http://www.scopus.com/inward/record.url?scp=79151479590&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=79151479590&partnerID=8YFLogxK
U2 - 10.1016/j.ydbio.2010.11.032
DO - 10.1016/j.ydbio.2010.11.032
M3 - Article
C2 - 21145317
AN - SCOPUS:79151479590
SN - 0012-1606
VL - 350
SP - 290
EP - 300
JO - Developmental biology
JF - Developmental biology
IS - 2
ER -