PMID- 27058886
OWN - NLM
STAT- MEDLINE
DCOM- 20160826
LR  - 20240327
IS  - 1553-7404 (Electronic)
IS  - 1553-7390 (Print)
IS  - 1553-7390 (Linking)
VI  - 12
IP  - 4
DP  - 2016 Apr
TI  - Genetic Dissection of Dual Roles for the Transcription Factor six7 in 
      Photoreceptor Development and Patterning in Zebrafish.
PG  - e1005968
LID - 10.1371/journal.pgen.1005968 [doi]
LID - e1005968
AB  - The visual system of a particular species is highly adapted to convey detailed 
      ecological and behavioral information essential for survival. The consequences of 
      structural mutations of opsins upon spectral sensitivity and environmental 
      adaptation have been studied in great detail, but lacking is knowledge of the 
      potential influence of alterations in gene regulatory networks upon the diversity 
      of cone subtypes and the variation in the ratio of rods and cones observed in 
      numerous diurnal and nocturnal species. Exploiting photoreceptor patterning in 
      cone-dominated zebrafish, we uncovered two independent mechanisms by which the 
      sine oculis homeobox homolog 7 (six7) regulates photoreceptor development. In a 
      genetic screen, we isolated the lots-of-rods-junior (ljrp23ahub) mutation that 
      resulted in an increased number and uniform distribution of rods in otherwise 
      normal appearing larvae. Sequence analysis, genome editing using TALENs and 
      knockdown strategies confirm ljrp23ahub as a hypomorphic allele of six7, a 
      teleost orthologue of six3, with known roles in forebrain patterning and 
      expression of opsins. Based on the lack of predicted protein-coding changes and a 
      deletion of a conserved element upstream of the transcription start site, a 
      cis-regulatory mutation is proposed as the basis of the reduced expression of 
      six7 in ljrp23ahub. Comparison of the phenotypes of the hypomorphic and knock-out 
      alleles provides evidence of two independent roles in photoreceptor development. 
      EdU and PH3 labeling show that the increase in rod number is associated with 
      extended mitosis of photoreceptor progenitors, and TUNEL suggests that the lack 
      of green-sensitive cones is the result of cell death of the cone precursor. These 
      data add six7 to the small but growing list of essential genes for specification 
      and patterning of photoreceptors in non-mammalian vertebrates, and highlight 
      alterations in transcriptional regulation as a potential source of photoreceptor 
      variation across species.
FAU - Sotolongo-Lopez, Mailin
AU  - Sotolongo-Lopez M
AD  - Department of Biological Science, The Florida State University, Tallahassee, 
      Florida, United States of America.
FAU - Alvarez-Delfin, Karen
AU  - Alvarez-Delfin K
AD  - Department of Biological Science, The Florida State University, Tallahassee, 
      Florida, United States of America.
FAU - Saade, Carole J
AU  - Saade CJ
AD  - Department of Biological Science, The Florida State University, Tallahassee, 
      Florida, United States of America.
AD  - Program in Neuroscience, The Florida State University, Tallahassee, Florida, 
      United States of America.
FAU - Vera, Daniel L
AU  - Vera DL
AD  - Center for Genomics and Personalized Medicine, The Florida State University, 
      Tallahassee, Florida, United States of America.
FAU - Fadool, James M
AU  - Fadool JM
AD  - Department of Biological Science, The Florida State University, Tallahassee, 
      Florida, United States of America.
AD  - Program in Neuroscience, The Florida State University, Tallahassee, Florida, 
      United States of America.
LA  - eng
GR  - F31 EY020106/EY/NEI NIH HHS/United States
GR  - R01 EY017753/EY/NEI NIH HHS/United States
GR  - R01 RR020357/RR/NCRR NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20160408
PL  - United States
TA  - PLoS Genet
JT  - PLoS genetics
JID - 101239074
RN  - 0 (Homeodomain Proteins)
RN  - 0 (Six7 protein, zebrafish)
RN  - 0 (Zebrafish Proteins)
SB  - IM
MH  - Alleles
MH  - Animals
MH  - *Body Patterning
MH  - Homeodomain Proteins/genetics/*physiology
MH  - Photoreceptor Cells, Vertebrate/*metabolism
MH  - Zebrafish/*embryology
MH  - Zebrafish Proteins/genetics/*physiology
PMC - PMC4825938
COIS- The authors have declared that no competing interests exist.
EDAT- 2016/04/09 06:00
MHDA- 2016/08/27 06:00
PMCR- 2016/04/08
CRDT- 2016/04/09 06:00
PHST- 2015/11/16 00:00 [received]
PHST- 2016/03/09 00:00 [accepted]
PHST- 2016/04/09 06:00 [entrez]
PHST- 2016/04/09 06:00 [pubmed]
PHST- 2016/08/27 06:00 [medline]
PHST- 2016/04/08 00:00 [pmc-release]
AID - PGENETICS-D-15-02805 [pii]
AID - 10.1371/journal.pgen.1005968 [doi]
PST - epublish
SO  - PLoS Genet. 2016 Apr 8;12(4):e1005968. doi: 10.1371/journal.pgen.1005968. 
      eCollection 2016 Apr.