PURPOSE: The purpose of this study was to determine the intracellular pathways by which ciliary neurotrophic factor (CNTF) and leukemia inhibitory factor (LIF) negatively regulate the development of rod photoreceptors in the mouse retina. METHODS: Retina explant cultures derived from timed-pregnant CD-1 mice were used to monitor rod photoreceptor differentiation. CNTF was used to activate the signal transducer and activator of transcription (STAT)-3 and mitogen-activated protein kinase (MAPK) signal transduction pathways. Activation of STAT3 and MAPK were manipulated by using dominant-negative STAT3 recombinant adenoviruses and a specific inhibitor of MAPK, respectively. Explanted retinas were harvested at distinct time points and processed for immunohistochemistry. RESULTS: Blocking of the MAPK pathway by the MAPK inhibitor PD98059 did not affect normal development of rods in retina explants or the suppression of their appearance by treatment with CNTF. In contrast, activated STAT3 was necessary for suppression of the rod cell fate decision. A deficiency of the STAT3 pathway induced by a dominant negative STAT3 abolished inhibition of rod development by CNTF. CONCLUSIONS: These results indicate that STAT3, but not MAPK, can critically regulate photoreceptor development during mouse retina development.
PURPOSE: The purpose of this study was to determine the intracellular pathways by which ciliary neurotrophic factor (CNTF) and leukemia inhibitory factor (LIF) negatively regulate the development of rod photoreceptors in the mouse retina. METHODS: Retina explant cultures derived from timed-pregnant CD-1mice were used to monitor rod photoreceptor differentiation. CNTF was used to activate the signal transducer and activator of transcription (STAT)-3 and mitogen-activated protein kinase (MAPK) signal transduction pathways. Activation of STAT3 and MAPK were manipulated by using dominant-negative STAT3 recombinant adenoviruses and a specific inhibitor of MAPK, respectively. Explanted retinas were harvested at distinct time points and processed for immunohistochemistry. RESULTS: Blocking of the MAPK pathway by the MAPK inhibitor PD98059 did not affect normal development of rods in retina explants or the suppression of their appearance by treatment with CNTF. In contrast, activated STAT3 was necessary for suppression of the rod cell fate decision. A deficiency of the STAT3 pathway induced by a dominant negative STAT3 abolished inhibition of rod development by CNTF. CONCLUSIONS: These results indicate that STAT3, but not MAPK, can critically regulate photoreceptor development during mouse retina development.
Authors: Andrea Angius; Paolo Uva; Insa Buers; Manuela Oppo; Alessandro Puddu; Stefano Onano; Ivana Persico; Angela Loi; Loredana Marcia; Wolfgang Höhne; Gianmauro Cuccuru; Giorgio Fotia; Manila Deiana; Mara Marongiu; Hatice Tuba Atalay; Sibel Inan; Osama El Assy; Leo M E Smit; Ilyas Okur; Koray Boduroglu; Gülen Eda Utine; Esra Kılıç; Giuseppe Zampino; Giangiorgio Crisponi; Laura Crisponi; Frank Rutsch Journal: Am J Hum Genet Date: 2016-07-07 Impact factor: 11.025
Authors: Evgenya Y Popova; Sergei A Grigoryev; Yuhong Fan; Arthur I Skoultchi; Samuel S Zhang; Colin J Barnstable Journal: J Biol Chem Date: 2013-05-03 Impact factor: 5.157
Authors: Evgenya Y Popova; Carolina Pinzon-Guzman; Anna C Salzberg; Samuel Shao-Min Zhang; Colin J Barnstable Journal: Mol Neurobiol Date: 2015-08-23 Impact factor: 5.590