TY - JOUR
T1 - Expression profiling of zebrafish sox9 mutants reveals that Sox9 is required for retinal differentiation
AU - Yokoi, Hayato
AU - Yan, Yi Lin
AU - Miller, Michael R.
AU - BreMiller, Ruth A.
AU - Catchen, Julian M.
AU - Johnson, Eric A.
AU - Postlethwait, John H.
N1 - Funding Information:
We thank Steve Johnson and John Rawls for kindly providing the microarray, and Bruce Barut and Len Zon for sending us the klf2b plasmid, the Zebrafish International Resource Center (ZIRC, supported by grant P40 RR012546 from the NIH-NCRR) for providing the antibody zpr-3. We thank Joy Murphy, Amber Starks, Amanda Rapp and the University of Oregon Zebrafish Facility for providing animals and excellent fish care, and Poh Kheng Loi and Amber Selix of the Histology Facility for sectioning, and Jerry Gleason of the Bio-Optics Lab for help. We are grateful to the University of Oregon zebrafish ‘groupie’ attendees for helpful and friendly input. This work was supported by the National Center for Research Resources (5R01RR020833) and National Institutes of Health (P01 HD22486); the contents of this study are solely the responsibility of the authors and do not necessarily represent the official views of NCRR or NIH.
PY - 2009/5/1
Y1 - 2009/5/1
N2 - The transcription factor gene Sox9 plays various roles in development, including differentiation of the skeleton, gonads, glia, and heart. Other functions of Sox9 remain enigmatic. Because Sox9 protein regulates expression of target genes, the identification of Sox9 targets should facilitate an understanding of the mechanisms of Sox9 action. To help identify Sox9 targets, we used microarray expression profiling to compare wild-type embryos to mutant embryos lacking activity for both sox9a and sox9b, the zebrafish co-orthologs of Sox9. Candidate genes were further evaluated by whole-mount in situ hybridization in wild-type and sox9 single and double mutant embryos. Results identified genes expressed in cartilage (col2a1a and col11a2), retina (calb2a, calb2b, crx, neurod, rs1, sox4a and vsx1) and pectoral fin bud (klf2b and EST AI722369) as candidate targets for Sox9. Cartilage is a well-characterized Sox9 target, which validates this strategy, whereas retina represents a novel Sox9 function. Analysis of mutant phenotypes confirmed that Sox9 helps regulate the number of Müller glia and photoreceptor cells and helps organize the neural retina. These roles in eye development were previously unrecognized and reinforce the multiple functions that Sox9 plays in vertebrate development.
AB - The transcription factor gene Sox9 plays various roles in development, including differentiation of the skeleton, gonads, glia, and heart. Other functions of Sox9 remain enigmatic. Because Sox9 protein regulates expression of target genes, the identification of Sox9 targets should facilitate an understanding of the mechanisms of Sox9 action. To help identify Sox9 targets, we used microarray expression profiling to compare wild-type embryos to mutant embryos lacking activity for both sox9a and sox9b, the zebrafish co-orthologs of Sox9. Candidate genes were further evaluated by whole-mount in situ hybridization in wild-type and sox9 single and double mutant embryos. Results identified genes expressed in cartilage (col2a1a and col11a2), retina (calb2a, calb2b, crx, neurod, rs1, sox4a and vsx1) and pectoral fin bud (klf2b and EST AI722369) as candidate targets for Sox9. Cartilage is a well-characterized Sox9 target, which validates this strategy, whereas retina represents a novel Sox9 function. Analysis of mutant phenotypes confirmed that Sox9 helps regulate the number of Müller glia and photoreceptor cells and helps organize the neural retina. These roles in eye development were previously unrecognized and reinforce the multiple functions that Sox9 plays in vertebrate development.
KW - Calb2
KW - Col11a2
KW - Evolution of gene function
KW - Microarray
KW - Müller glia
KW - Photoreceptor
KW - Transcription factor
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U2 - 10.1016/j.ydbio.2009.01.002
DO - 10.1016/j.ydbio.2009.01.002
M3 - Article
C2 - 19210963
AN - SCOPUS:64049090578
SN - 0012-1606
VL - 329
SP - 1
EP - 15
JO - Developmental Biology
JF - Developmental Biology
IS - 1
ER -