PMID- 33788836
OWN - NLM
STAT- MEDLINE
DCOM- 20210802
LR  - 20220108
IS  - 1553-7404 (Electronic)
IS  - 1553-7390 (Print)
IS  - 1553-7390 (Linking)
VI  - 17
IP  - 3
DP  - 2021 Mar
TI  - Doublesex regulates fruitless expression to promote sexual dimorphism of the 
      gonad stem cell niche.
PG  - e1009468
LID - 10.1371/journal.pgen.1009468 [doi]
LID - e1009468
AB  - Doublesex (Dsx) and Fruitless (Fru) are the two downstream transcription factors 
      that actuate Drosophila sex determination. While Dsx assists Fru to regulate 
      sex-specific behavior, whether Fru collaborates with Dsx in regulating other 
      aspects of sexual dimorphism remains unknown. One important aspect of sexual 
      dimorphism is found in the gonad stem cell (GSC) niches, where male and female 
      GSCs are regulated to create large numbers of sperm and eggs. Here we report that 
      Fru is expressed male-specifically in the GSC niche and plays important roles in 
      the development and maintenance of these cells. Unlike previously-studied aspects 
      of sex-specific Fru expression, which are regulated by Transformer (Tra)-mediated 
      alternative splicing, we show that male-specific expression of fru in the gonad 
      is regulated downstream of dsx, and is independent of tra. fru genetically 
      interacts with dsx to support maintenance of the niche throughout development. 
      Ectopic expression of fru inhibited female niche formation and partially 
      masculinized the ovary. fru is also required autonomously for cyst stem cell 
      maintenance and cyst cell survival. Finally, we identified a conserved Dsx 
      binding site upstream of fru promoter P4 that regulates fru expression in the 
      niche, indicating that fru is likely a direct target for transcriptional 
      regulation by Dsx. These findings demonstrate that fru acts outside the nervous 
      system to influence sexual dimorphism and reveal a new mechanism for regulating 
      sex-specific expression of fru that is regulated at the transcriptional level by 
      Dsx, rather than by alternative splicing by Tra.
FAU - Zhou, Hong
AU  - Zhou H
AUID- ORCID: 0000-0002-3273-2420
AD  - Department of Biology, Johns Hopkins University, 3400 N. Charles Street, 
      Baltimore, MD, United States of America.
FAU - Whitworth, Cale
AU  - Whitworth C
AUID- ORCID: 0000-0003-1963-5850
AD  - Department of Biology, Johns Hopkins University, 3400 N. Charles Street, 
      Baltimore, MD, United States of America.
FAU - Pozmanter, Caitlin
AU  - Pozmanter C
AUID- ORCID: 0000-0001-5143-3955
AD  - Department of Biology, Johns Hopkins University, 3400 N. Charles Street, 
      Baltimore, MD, United States of America.
FAU - Neville, Megan C
AU  - Neville MC
AUID- ORCID: 0000-0001-8506-9944
AD  - Centre for Neural Circuits and Behaviour, University of Oxford, Tinsley Building, 
      Mansfield Road, Oxford, United Kingdom.
FAU - Van Doren, Mark
AU  - Van Doren M
AUID- ORCID: 0000-0002-5475-003X
AD  - Department of Biology, Johns Hopkins University, 3400 N. Charles Street, 
      Baltimore, MD, United States of America.
LA  - eng
GR  - P40 OD018537/OD/NIH HHS/United States
GR  - R01 GM113001/GM/NIGMS NIH HHS/United States
GR  - T32 GM007231/GM/NIGMS NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, U.S. Gov't, Non-P.H.S.
DEP - 20210331
PL  - United States
TA  - PLoS Genet
JT  - PLoS genetics
JID - 101239074
RN  - 0 (Drosophila Proteins)
RN  - 0 (Nerve Tissue Proteins)
RN  - 0 (Transcription Factors)
RN  - 0 (fru protein, Drosophila)
SB  - IM
MH  - Animals
MH  - Drosophila Proteins/*genetics/metabolism
MH  - Evolution, Molecular
MH  - Female
MH  - Fluorescent Antibody Technique
MH  - *Gene Expression Regulation
MH  - Gene Order
MH  - Genetic Loci
MH  - Gonads/*cytology/*metabolism
MH  - Male
MH  - Nerve Tissue Proteins/*genetics/metabolism
MH  - *Sex Characteristics
MH  - Sex Determination Processes/*genetics
MH  - Stem Cell Niche/*genetics
MH  - Stem Cells/*metabolism
MH  - Testis
MH  - Transcription Factors/*genetics/metabolism
PMC - PMC8041189
COIS- The authors have declared that no competing interests exist.
EDAT- 2021/04/01 06:00
MHDA- 2021/08/03 06:00
PMCR- 2021/03/31
CRDT- 2021/03/31 17:17
PHST- 2020/05/22 00:00 [received]
PHST- 2021/03/04 00:00 [accepted]
PHST- 2021/04/12 00:00 [revised]
PHST- 2021/04/01 06:00 [pubmed]
PHST- 2021/08/03 06:00 [medline]
PHST- 2021/03/31 17:17 [entrez]
PHST- 2021/03/31 00:00 [pmc-release]
AID - PGENETICS-D-20-00524 [pii]
AID - 10.1371/journal.pgen.1009468 [doi]
PST - epublish
SO  - PLoS Genet. 2021 Mar 31;17(3):e1009468. doi: 10.1371/journal.pgen.1009468. 
      eCollection 2021 Mar.