How to Make a Rod Photoreceptor:The Role of bZIP Transcription Factor NRL in Retinal Development.

Retina;Photoreceptor;Molecular;Cellular and Developmental Biology;Science;Neuroscience

Oh, EdwinTurner, David ;

University of Michigan

关键词: Retina;    Photoreceptor;    Molecular;    Cellular and Developmental Biology;    Science;    Neuroscience;   

Others  :  https://deepblue.lib.umich.edu/bitstream/handle/2027.42/60860/edwinoh_1.pdf?sequence=1&isAllowed=y

瑞士|英语

来源: The Illinois Digital Environment for Access to Learning and Scholarship

【 摘 要 】

During the development of the mammalian retina, neuroepithelial progenitors are proposed to pass through a series of competence states and give rise to different cell types on a predictable schedule.The mechanism(s) by which multipotent progenitors respond to intrinsic factors and/or extrinsic signals and differentiate into mature neurons are poorly understood.The neural retina leucine zipper protein (NRL), a bZIP transcription factor of the Maf subfamily, is a key regulator of developmental processes in the mammalian retina.The goal of my dissertation is to investigate how NRL modulates photoreceptor cell fate decisions.In the first part of my dissertation, I tested the hypothesis that NRL plays an instructive role in determining rod photoreceptor fate.To accomplish this, I generated a series of transgenic mouse lines that ectopically express NRL in early post-mitotic photoreceptor precursors or in presumptive cone photoreceptors using the Crx or the S-opsin promoter, respectively.My studies reveal that expression of NRL results in complete transformation of cone precursors to functional rod photoreceptors.This research provided direct in vivo evidence of post-mitotic developmental and synaptic plasticity in the developing mammalian retina.To investigate the epistatic relationship between NRL and NR2E3, I generated a transgenic mouse line in which cone precursors express NRL but not NR2E3.Interestingly, ectopic expression of NRL can partially repress S-opsin, but not M-opsin, expression even in the absence of NR2E3.These and additional studies suggest that simultaneous expression of NRL and NR2E3 is required to promote functional rod differentiation and to suppress cone development.As both rods and cones connect to horizontal cells (HCs) in the retina, we wanted to understand whether the differentiation of HCs is affected by the absence of afferent neurons by examining Nrl-/- (rodless) and Crxp-Nrl (coneless) mice.Our studies reveal that the morphology of the HC axon terminal system or dendritic field of the HC is defined respectively by rods or cones.The major conclusions of my studies are that NRL plays an instructive role in rod photoreceptor development and that photoreceptor precursors are competent to make binary decisions in acquiring rod versus cone identity.