TY - JOUR
T1 - Drosophila Fragile X Protein controls cellular proliferation by regulating cbl levels in the ovary
AU - Epstein, Andrew M.
AU - Bauer, Christopher R.
AU - Ho, Aaron
AU - Bosco, Giovanni
AU - Zarnescu, Daniela C.
N1 - Funding Information:
We thank Frans Tax and members of the Zarnescu lab for comments on the manuscript, Terry Orr-Weaver (MIT) for anti-cyclin E antibodies, Trudi Schupbach (Princeton University) for the cbl F165 stock and useful discussions, Li Mei Pai (Chang-Gung University, Taiwan) for anti-Cbl antibodies, and Bloomington Stock Center and the DGRC for fly stocks and Gateway vectors, respectively. Barb Carolus and Paula Campbell (Flow Cytometry Facility) assisted with flow cytometry and Carl Boswell (MCB Imaging Facility) provided imaging support. We also thank Sara Clasen for help with testing the cbl F165 dFmr1 3 recombinant lines. The dFmr1 cDNA, the dFmr1 3 allele as well as the P[dFmr1+] genomic rescue line were provided by Tom Jongens (University of Pennsylvania). The dFmr1 50M allele was provided by Kendal Broadie (Vanderbilt University). Financial support was provided by the University of Arizona start-up funds and the Arizona Biomedical Research Commission (contract 0820) to DCZ and by NIH RO1 GM069462 to GB. CRB was funded in part by NSF IGERT in Genomics. AH was partly supported by the University of Arizona Undergraduate Biology Research Program funded by the Howard Hughes Medical Institute (#71196-521304).
PY - 2009/6/1
Y1 - 2009/6/1
N2 - FMRP is an RNA binding protein linked to the most common form of inherited mental retardation, Fragile X syndrome (FraX). In addition to severe cognitive deficits, FraX etiology includes postpubescent macroorchidism, which is thought to result from overproliferation. Using a Drosophila FraX model, we show that FMRP controls germline proliferation during oogenesis. dFmr1 null ovaries contain egg chambers with both fewer and supranumerary germ cells. The mutant germaria contain a significantly increased number of cyclin E and PhosphoHistone H3 positive cells, suggesting that loss of FMRP leads to defects in cell cycle progression. BrdU incorporation and flow cytometry data suggest that, in addition to proliferation, germline endoreplication and ploidy are also affected by the loss of FMRP during ovary development. Here we report that FMRP controls the levels of cbl mRNA in the ovary and that reducing cbl gene dosage by half rescues the dFmr1 oogenesis phenotypes. These data support a model whereby FMRP controls germline proliferation by regulating the expression of cbl in the developing ovary.
AB - FMRP is an RNA binding protein linked to the most common form of inherited mental retardation, Fragile X syndrome (FraX). In addition to severe cognitive deficits, FraX etiology includes postpubescent macroorchidism, which is thought to result from overproliferation. Using a Drosophila FraX model, we show that FMRP controls germline proliferation during oogenesis. dFmr1 null ovaries contain egg chambers with both fewer and supranumerary germ cells. The mutant germaria contain a significantly increased number of cyclin E and PhosphoHistone H3 positive cells, suggesting that loss of FMRP leads to defects in cell cycle progression. BrdU incorporation and flow cytometry data suggest that, in addition to proliferation, germline endoreplication and ploidy are also affected by the loss of FMRP during ovary development. Here we report that FMRP controls the levels of cbl mRNA in the ovary and that reducing cbl gene dosage by half rescues the dFmr1 oogenesis phenotypes. These data support a model whereby FMRP controls germline proliferation by regulating the expression of cbl in the developing ovary.
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U2 - 10.1016/j.ydbio.2009.03.011
DO - 10.1016/j.ydbio.2009.03.011
M3 - Article
C2 - 19306863
AN - SCOPUS:67349278796
SN - 0012-1606
VL - 330
SP - 83
EP - 92
JO - Developmental biology
JF - Developmental biology
IS - 1
ER -