The Ciliary Margin Zone of the Mammalian Retina Generates Retinal Ganglion Cells
Florencia Marcucci,
Veronica Murcia-Belmonte,
Qing Wang,
Yaiza Coca,
Susana Ferreiro-Galve,
Takaaki Kuwajima,
Sania Khalid,
M. Elizabeth Ross,
Carol Mason,
Eloisa Herrera
Affiliations
Florencia Marcucci
Department of Pathology and Cell Biology, College of Physicians and Surgeons, Columbia University, New York, NY 10032, USA
Veronica Murcia-Belmonte
Instituto de Neurociencias de Alicante (Consejo Superior de Investigaciones Científicas-Universidad Miguel Hernández), 03550 Sant Joan d’Alacant, Spain
Qing Wang
Department of Pathology and Cell Biology, College of Physicians and Surgeons, Columbia University, New York, NY 10032, USA
Yaiza Coca
Instituto de Neurociencias de Alicante (Consejo Superior de Investigaciones Científicas-Universidad Miguel Hernández), 03550 Sant Joan d’Alacant, Spain
Susana Ferreiro-Galve
Instituto de Neurociencias de Alicante (Consejo Superior de Investigaciones Científicas-Universidad Miguel Hernández), 03550 Sant Joan d’Alacant, Spain
Takaaki Kuwajima
Department of Pathology and Cell Biology, College of Physicians and Surgeons, Columbia University, New York, NY 10032, USA
Sania Khalid
Department of Pathology and Cell Biology, College of Physicians and Surgeons, Columbia University, New York, NY 10032, USA
M. Elizabeth Ross
Center for Neurogenetics, Feil Family Brain & Mind Research Institute, Weill Cornell Medical College, New York, NY 10021, USA
Carol Mason
Department of Pathology and Cell Biology, College of Physicians and Surgeons, Columbia University, New York, NY 10032, USA
Eloisa Herrera
Instituto de Neurociencias de Alicante (Consejo Superior de Investigaciones Científicas-Universidad Miguel Hernández), 03550 Sant Joan d’Alacant, Spain
The retina of lower vertebrates grows continuously by integrating new neurons generated from progenitors in the ciliary margin zone (CMZ). Whether the mammalian CMZ provides the neural retina with retinal cells is controversial. Live imaging of embryonic retina expressing eGFP in the CMZ shows that cells migrate laterally from the CMZ to the neural retina where differentiated retinal ganglion cells (RGCs) reside. Because Cyclin D2, a cell-cycle regulator, is enriched in ventral CMZ, we analyzed Cyclin D2−/− mice to test whether the CMZ is a source of retinal cells. Neurogenesis is diminished in Cyclin D2 mutants, leading to a reduction of RGCs in the ventral retina. In line with these findings, in the albino retina, the decreased production of ipsilateral RGCs is correlated with fewer Cyclin D2+ cells. Together, these results implicate the mammalian CMZ as a neurogenic site that produces RGCs and whose proper generation depends on Cyclin D2 activity.
