Downregulation of STAT3 activation is required for presumptive rod photoreceptor cells to differentiate in the postnatal retina.
Ciliary neurotrophic factor (CNTF) has been known to inhibit the differentiation of presumptive rod photoreceptor cells; however, the underlying mechanisms have remained to be elucidated. We demonstrated that STAT3 activation, but not SHP2 activation, is responsible for the CNTF/gp130 signaling that inhibits expression of Rhodopsin and its upstream activator, crx, in the retinal explants derived from P0 mice (P0 retinal explants), utilizing STAT3-deficient retina and electroporation of dominant-negative form of STAT3 (STAT3F). We also demonstrated that STAT3 activation in presumptive rod photoreceptor cells at E18.5 is rapidly downregulated at P0, when Rhodopsin expression starts during retinal development. Persistent STAT3 activation in the P0 retinal explants prevented Rhodopsin expression and rapid upregulation of crx expression. STAT3-deficient retinas did not exhibit precocious rod photoreceptor cell differentiation as a whole, although they occasionally exhibited precocious upregulation of crx mRNA. Thus, we conclude that downregulation of STAT3 activation is required, but insufficient, for rod photoreceptor cell differentiation in the postnatal retina.
Ozawa
Yoko
Y
Department of Physiology, Keio University School of Medicine, Shinjuku, Tokyo, Japan.
Nakao
Keiko
K
Shimazaki
Takuya
T
Takeda
Junji
J
Akira
Shizuo
S
Ishihara
Katsuhiko
K
Hirano
Toshio
T
Oguchi
Yoshihisa
Y
Okano
Hideyuki
H
D000818:Animals; D000831:Animals, Newborn; D002454:Cell Differentiation / Q000235:genetics; D002478:Cells, Cultured; D020934:Ciliary Neurotrophic Factor / Q000378:metabolism*; D058966:Contactins; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D015536:Down-Regulation / Q000235:genetics*; D018507:Gene Expression Regulation, Developmental / Q000235:genetics*; D018398:Homeodomain Proteins / Q000235:genetics / Q000378:metabolism; D047908:Intracellular Signaling Peptides and Proteins; D051379:Mice; D008810:Mice, Inbred C57BL; D008813:Mice, Inbred ICR; D019006:Neural Cell Adhesion Molecules / Q000378:metabolism; D054592:Protein Tyrosine Phosphatase, Non-Receptor Type 11; D017027:Protein Tyrosine Phosphatases / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D017948:Retinal Rod Photoreceptor Cells / Q000166:cytology / Q000254:growth & development / Q000378:metabolism*; D012243:Rhodopsin / Q000235:genetics / Q000378:metabolism; D050796:STAT3 Transcription Factor; D015534:Trans-Activators / Q000235:genetics / Q000378:metabolism*; D015854:Up-Regulation / Q000235:genetics
D020934:Ciliary Neurotrophic Factor; D058966:Contactins; D004268:DNA-Binding Proteins; D018398:Homeodomain Proteins; D047908:Intracellular Signaling Peptides and Proteins; D019006:Neural Cell Adhesion Molecules; D012333:RNA, Messenger; D050796:STAT3 Transcription Factor; C494087:Stat3 protein, mouse; D015534:Trans-Activators; C109288:cone rod homeobox protein; D012243:Rhodopsin; D054592:Protein Tyrosine Phosphatase, Non-Receptor Type 11; D017027:Protein Tyrosine Phosphatases; C516725:Ptpn11 protein, mouse