p57(Kip2) regulates progenitor cell proliferation and amacrine interneuron development in the mouse retina

Development ◽  
2000 ◽  
Vol 127 (16) ◽  
pp. 3593-3605 ◽  
Author(s):  
M.A. Dyer ◽  
C.L. Cepko
Keyword(s):  
Cell Cycle ◽  
Progenitor Cells ◽  
Kinase Inhibitor ◽  
Retinal Development ◽  
Cell Types ◽  
Cell Cycle Exit ◽  
Retinal Progenitor Cells ◽  
Mouse Development ◽  
Retinal Progenitor ◽  
Cyclin Kinase Inhibitor

A precise balance between proliferation and differentiation must be maintained during retinal development to obtain the correct proportion of each of the seven cell types found in the adult tissue. Cyclin kinase inhibitors can regulate cell cycle exit coincident with induction of differentiation programs during development. We have found that the p57(Kip2) cyclin kinase inhibitor is upregulated during G(1)/G(0) in a subset of retinal progenitor cells exiting the cell cycle between embryonic day 14.5 and 16.5 of mouse development. Retroviral mediated overexpression of p57(Kip2) in embryonic retinal progenitor cells led to premature cell cycle exit. Retinae from mice lacking p57(Kip2) exhibited inappropriate S-phase entry and apoptotic nuclei were found in the region where p57(Kip2) is normally expressed. Apoptosis precisely compensated for the inappropriate proliferation in the p57(Kip2)-deficient retinae to preserve the correct proportion of the major retinal cell types. Postnatally, p57(Kip2) was found to be expressed in a novel subpopulation of amacrine interneurons. At this stage, p57(Kip2)did not regulate proliferation. However, perhaps reflecting its role during this late stage of development, animals lacking p57(Kip2) showed an alteration in amacrine subpopulations. p57(Kip2) is the first gene to be implicated as a regulator of amacrine subtype/subpopulation development. Consequently, we propose that p57(Kip2) has two roles during retinal development, acting first as a cyclin kinase inhibitor in mitotic progenitor cells, and then playing a distinct role in neuronal differentiation.

scholarly journals Co-ordinating retinal histogenesis: early cell cycle exit enhances early cell fate determination in the Xenopus retina

Development ◽  
2002 ◽  
Vol 129 (10) ◽  
pp. 2435-2446 ◽  
Author(s):  
Shin-ichi Ohnuma ◽  
Susannah Hopper ◽  
Kevin C. Wang ◽  
Anna Philpott ◽  
William A. Harris
Keyword(s):  
Cell Cycle ◽  
Cell Fate ◽  
Kinase Inhibitor ◽  
Cell Types ◽  
Retinal Ganglion ◽  
Cell Cycle Exit ◽  
Cyclin E1 ◽  
Distinct Cell ◽  
Cyclin Kinase Inhibitor ◽  
Notch Activation

The laminar arrays of distinct cell types in the vertebrate retina are built by a histogenic process in which cell fate is correlated with birth order. To explore this co-ordination mechanistically, we altered the relative timing of cell cycle exit in the developing Xenopus retina and asked whether this affected the activity of neural determinants. We found that Xath5, a bHLH proneural gene that promotes retinal ganglion cell (RGC) fate, (Kanekar, S., Perron, M., Dorsky, R., Harris, W. A., Jan, L. Y., Jan, Y. N. and Vetter, M. L. (1997) Neuron19, 981-994), does not cause these cells to be born prematurely. To drive cells out of the cell cycle early, therefore, we misexpressed the cyclin kinase inhibitor, p27Xic1. We found that early cell cycle exit potentiates the ability of Xath5 to promote RGC fate. Conversely, the cell cycle activator, cyclin E1, which inhibits cell cycle exit, biases Xath5-expressing cells toward later neuronal fates. We found that Notch activation in this system caused cells to exit the cell cycle prematuely, and when it is misexpressed with Xath5, it also potentiates the induction of RGCs. The potentiation is counteracted by co-expression of cyclin E1. These results suggest a model of histogenesis in which the activity of factors that promote early cell cycle exit enhances the activity of factors that promote early cellular fates.

scholarly journals Pax6 Is Required for Normal Cell-Cycle Exit and the Differentiation Kinetics of Retinal Progenitor Cells

PLoS ONE ◽  
2013 ◽  
Vol 8 (9) ◽  
pp. e76489 ◽  
Author(s):  
Chen Farhy ◽  
Michael Elgart ◽  
Zehavit Shapira ◽  
Varda Oron-Karni ◽  
Orly Yaron ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Progenitor Cells ◽  
Normal Cell ◽  
Cell Cycle Exit ◽  
Retinal Progenitor Cells ◽  
Retinal Progenitor ◽  
Kinetics Of ◽  
Normal Cell Cycle

scholarly journals Notch signaling represses cone photoreceptor formation through the regulation of retinal progenitor cell states

2020 ◽  
Author(s):  
Xueqing Chen ◽  
Mark M. Emerson
Keyword(s):  
Cell Cycle ◽  
Notch Signaling ◽  
Progenitor Cells ◽  
Progenitor Cell ◽  
State Transitions ◽  
Proliferative Potential ◽  
Primary Role ◽  
Cone Photoreceptor ◽  
Retinal Progenitor Cells ◽  
Retinal Progenitor

AbstractVertebrate cone photoreceptor formation is a multistep process. First, multipotent retinal progenitor cells generate genetically-defined restricted/neurogenic progenitor cells and these cells then divide to preferentially produce cones and horizontal cells. Notch signaling represses cone formation and maintains the proliferative potential of retinal progenitor cells. However, the mechanisms through which it affects these processes are unknown. Here we use cell type specific inhibition of Notch signaling to localize the primary role of Notch signaling during cone genesis to the regulation of restricted retinal progenitor cells from multipotent retinal progenitor cells. Notch signaling inhibition in restricted progenitor cells does not alter the number of cones derived from these cells but does affect horizontal cell development. Cell cycle promotion is not a primary effect of Notch signaling but an indirect effect on progenitor cell state transitions that leads to depletion of the multipotent progenitor cell population. Taken together, this suggests that the roles of Notch in cone photoreceptor formation and cell cycle promotion are both mediated by a localized function in multipotent retinal progenitor cells to repress the formation of restricted progenitor cells.

scholarly journals Human retinal organoids release extracellular vesicles that regulate gene expression in target human retinal progenitor cells

2021 ◽  
Author(s):  
Jing Zhou ◽  
Miguel Flores-Bellver ◽  
Jianbo Pan ◽  
Alberto Benito-Martin ◽  
Cui Shi ◽  
...  
Keyword(s):  
Gene Expression ◽  
Progenitor Cells ◽  
Extracellular Vesicles ◽  
Noncoding Rna ◽  
Tissue Characterization ◽  
Retinal Development ◽  
Retinal Progenitor Cells ◽  
Retina Development ◽  
Retinal Tissue ◽  
Retinal Progenitor

AbstractThe mechanisms underlying retinal development have not been completely elucidated. Extracellular vesicles (EVs) are novel essential mediators of cell-to-cell communication with emerging roles in developmental processes. Nevertheless, the identification of EVs in human retinal tissue, characterization of their cargo, and analysis of their potential role in retina development has not been accomplished. Three-dimensional retinal tissue derived from human induced pluripotent stem cells (hiPSC) provide an ideal developmental system to achieve this goal. Here we report that hiPSC-derived retinal organoids release exosomes and microvesicles with small noncoding RNA cargo. EV miRNA cargo-predicted targetome correlates with GO pathways involved in mechanisms of retinogenesis relevant to specific developmental stages corresponding to hallmarks of native human retina development. Furthermore, uptake of EVs by human retinal progenitor cells leads to changes in gene expression correlated with EV miRNA cargo predicted gene targets, and mechanisms involved in retinal development, ganglion cell and photoreceptor differentiation and function.

A role for CK2 upon interkinetic nuclear migration in the cell cycle of retinal progenitor cells

2008 ◽  
Vol 68 (5) ◽  
pp. 620-631 ◽  
Author(s):  
Ana Carolina Dudenhoeffer Carneiro ◽  
Lucianne Fragel-Madeira ◽  
Mario Alberto Silva-Neto ◽  
Rafael Linden
Keyword(s):  
Cell Cycle ◽  
Progenitor Cells ◽  
Nuclear Migration ◽  
Retinal Progenitor Cells ◽  
Retinal Progenitor ◽  
Interkinetic Nuclear Migration

scholarly journals ARS2 is required for retinal progenitor cell S-phase progression and Müller glial cell fate specification

2020 ◽  
Vol 98 (1) ◽  
pp. 50-60 ◽  
Author(s):  
Connor O’Sullivan ◽  
Philip E.B. Nickerson ◽  
Oliver Krupke ◽  
Jennifer Christie ◽  
Li-Li Chen ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Progenitor Cells ◽  
Cell Fate ◽  
Cell Cycle Progression ◽  
S Phase ◽  
Cell Fate Specification ◽  
Retinal Progenitor Cells ◽  
Cycle Progression ◽  
Fate Specification ◽  
Retinal Progenitor

During a developmental period that extends postnatally in the mouse, proliferating multipotent retinal progenitor cells produce one of 7 major cell types (rod, cone, bipolar, horizontal, amacrine, ganglion, and Müller glial cells) as they exit the cell cycle in consecutive waves. Cell production in the retina is tightly regulated by intrinsic, extrinsic, spatial, and temporal cues, and is coupled to the timing of cell cycle exit. Arsenic-resistance protein 2 (ARS2, also known as SRRT) is a component of the nuclear cap-binding complex involved in RNA Polymerase II transcription, and is required for cell cycle progression. We show that postnatal retinal progenitor cells (RPCs) require ARS2 for proper progression through S phase, and ARS2 disruption leads to early exit from the cell cycle. Furthermore, we observe an increase in the proportion of cells expressing a rod photoreceptor marker, and a loss of Müller glia marker expression, indicating a role for ARS2 in regulating cell fate specification or differentiation. Knockdown of Flice Associated Huge protein (FLASH), which interacts with ARS2 and is required for cell cycle progression and 3′-end processing of replication-dependent histone transcripts, phenocopies ARS2 knockdown. These data implicate ARS2–FLASH-mediated histone mRNA processing in regulating RPC cell cycle kinetics and neuroglial cell fate specification during postnatal retinal development.

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