TY - JOUR
T1 - Pax6 is required for the multipotent state of retinal progenitor cells
AU - Marquardt, Till
AU - Ashery-Padan, Ruth
AU - Andrejewski, Nicole
AU - Scardigli, Raffaella
AU - Guillemot, Francois
AU - Gruss, Peter
N1 - Funding Information:
For providing reagents, we are indebted to N. L. Brown for Math5, J. Johnson for Mash1-enhancer and Mash1 antibody, R. Kageyama for Hes-1, C. Koch for recoverin antibody, K. Rajewsky for Cre, G. Bernier for Rx1, and X. Zhou for ires-gfp. We are especially grateful to G. Oliver for providing Six3 antibody prior to publication and to C. Lobe and A. Nagy for providing the Z/AP reporter line. We appreciate A. Stoykova, M. Kessel, and F. Cecconi for providing insightful comments on the manuscript. For helpful discussions and more, we acknowledge K. Chowdhury, M. Wagner, J. Berger, S. Bäumer, and A. Masselli, as well as H. Wässle and L. Gan for communicating results prior to publication. We finally appreciate S. Eckert, K. Müller, and N. Obermeyer for technical assistence, as well as U. Franke, R. Libal, and staff for microinjection and mouse work. R. A.-P. was supported by a long-term EMBO fellowship; R. S. by fellowships from the Italian Telethon Foundation and the EU TRM Program; and F. G. by institutional funds from INSERM-CNRS and Hôpital Universitarie de Strasbourg. This study was supported by EU grant B104-CT96-0042 and by the Max-Planck-Gesellschaft.
PY - 2001/4/6
Y1 - 2001/4/6
N2 - The molecular mechanisms mediating the retinogenic potential of multipotent retinal progenitor cells (RPCs) are poorly defined. Prior to initiating retinogenesis, RPCs express a limited set of transcription factors implicated in the evolutionary ancient genetic network that initiates eye development. We elucidated the function of one of these factors, Pax6, in the RPCs of the intact developing eye by conditional gene targeting. Upon Pax6 inactivation, the potential of RPCs becomes entirely restricted to only one of the cell fates normally available to RPCs, resulting in the exclusive generation of amacrine interneurons. Our findings demonstrate furthermore that Pax6 directly controls the transcriptional activation of retinogenic bHLH factors that bias subsets of RPCs toward the different retinal cell fates, thereby mediating the full retinogenic potential of RPCs.
AB - The molecular mechanisms mediating the retinogenic potential of multipotent retinal progenitor cells (RPCs) are poorly defined. Prior to initiating retinogenesis, RPCs express a limited set of transcription factors implicated in the evolutionary ancient genetic network that initiates eye development. We elucidated the function of one of these factors, Pax6, in the RPCs of the intact developing eye by conditional gene targeting. Upon Pax6 inactivation, the potential of RPCs becomes entirely restricted to only one of the cell fates normally available to RPCs, resulting in the exclusive generation of amacrine interneurons. Our findings demonstrate furthermore that Pax6 directly controls the transcriptional activation of retinogenic bHLH factors that bias subsets of RPCs toward the different retinal cell fates, thereby mediating the full retinogenic potential of RPCs.
UR - http://www.scopus.com/inward/record.url?scp=0035815295&partnerID=8YFLogxK
U2 - 10.1016/S0092-8674(01)00295-1
DO - 10.1016/S0092-8674(01)00295-1
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AN - SCOPUS:0035815295
VL - 105
SP - 43
EP - 55
JO - Cell
JF - Cell
SN - 0092-8674
IS - 1
ER -