Cargando…

Expanded progenitor populations, vitreo-retinal abnormalities, and Müller glial reactivity in the zebrafish leprechaun/patched2 retina

BACKGROUND: The roles of the Hedgehog (Hh) pathway in controlling vertebrate retinal development have been studied extensively; however, species- and context-dependent findings have provided differing conclusions. Hh signaling has been shown to control both population size and cell cycle kinetics of...

Descripción completa

Detalles Bibliográficos
Autores principales: Bibliowicz, Jonathan, Gross, Jeffrey M
Formato: Texto
Lenguaje:English
Publicado: BioMed Central 2009
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2770046/
https://www.ncbi.nlm.nih.gov/pubmed/19840373
http://dx.doi.org/10.1186/1471-213X-9-52
_version_ 1782173619299811328
author Bibliowicz, Jonathan
Gross, Jeffrey M
author_facet Bibliowicz, Jonathan
Gross, Jeffrey M
author_sort Bibliowicz, Jonathan
collection PubMed
description BACKGROUND: The roles of the Hedgehog (Hh) pathway in controlling vertebrate retinal development have been studied extensively; however, species- and context-dependent findings have provided differing conclusions. Hh signaling has been shown to control both population size and cell cycle kinetics of proliferating retinal progenitors, and to modulate differentiation within the retina by regulating the timing of cell cycle exit. While cell cycle exit has in turn been shown to control cell fate decisions within the retina, a direct role for the Hh pathway in retinal cell fate decisions has yet to be established in vivo. RESULTS: To gain further insight into Hh pathway function in the retina, we have analyzed retinal development in leprechaun/patched2 mutant zebrafish. While lep/ptc2 mutants possessed more cells in their retinas, all cell types, except for Müller glia, were present at identical ratios as those observed in wild-type siblings. lep/ptc2 mutants possessed a localized upregulation of GFAP, a marker for 'reactive' glia, as well as morphological abnormalities at the vitreo-retinal interface, where Müller glial endfeet terminate. In addition, analysis of the over-proliferation phenotype at the ciliary marginal zone (CMZ) revealed that the number of proliferating progenitors, but not the rate of proliferation, was increased in lep/ptc2 mutants. CONCLUSION: Our results indicate that Patched2-dependent Hh signaling does not likely play an integral role in neuronal cell fate decisions in the zebrafish retina. ptc2 deficiency in zebrafish results in defects at the vitreo-retinal interface and Müller glial reactivity. These phenotypes are similar to the ocular abnormalities observed in human patients suffering from Basal Cell Naevus Syndrome (BCNS), a disorder that has been linked to mutations in the human PTCH gene (the orthologue of the zebrafish ptc2), and point to the utility of the lep/ptc2 mutant line as a model for the study of BCNS-related ocular pathologies. Our findings regarding CMZ progenitor proliferation suggest that, in the zebrafish retina, Hh pathway activity may not affect cell cycle kinetics; rather, it likely regulates the size of the retinal progenitor pool in the CMZ.
format Text
id pubmed-2770046
institution National Center for Biotechnology Information
language English
publishDate 2009
publisher BioMed Central
record_format MEDLINE/PubMed
spelling pubmed-27700462009-10-29 Expanded progenitor populations, vitreo-retinal abnormalities, and Müller glial reactivity in the zebrafish leprechaun/patched2 retina Bibliowicz, Jonathan Gross, Jeffrey M BMC Dev Biol Research Article BACKGROUND: The roles of the Hedgehog (Hh) pathway in controlling vertebrate retinal development have been studied extensively; however, species- and context-dependent findings have provided differing conclusions. Hh signaling has been shown to control both population size and cell cycle kinetics of proliferating retinal progenitors, and to modulate differentiation within the retina by regulating the timing of cell cycle exit. While cell cycle exit has in turn been shown to control cell fate decisions within the retina, a direct role for the Hh pathway in retinal cell fate decisions has yet to be established in vivo. RESULTS: To gain further insight into Hh pathway function in the retina, we have analyzed retinal development in leprechaun/patched2 mutant zebrafish. While lep/ptc2 mutants possessed more cells in their retinas, all cell types, except for Müller glia, were present at identical ratios as those observed in wild-type siblings. lep/ptc2 mutants possessed a localized upregulation of GFAP, a marker for 'reactive' glia, as well as morphological abnormalities at the vitreo-retinal interface, where Müller glial endfeet terminate. In addition, analysis of the over-proliferation phenotype at the ciliary marginal zone (CMZ) revealed that the number of proliferating progenitors, but not the rate of proliferation, was increased in lep/ptc2 mutants. CONCLUSION: Our results indicate that Patched2-dependent Hh signaling does not likely play an integral role in neuronal cell fate decisions in the zebrafish retina. ptc2 deficiency in zebrafish results in defects at the vitreo-retinal interface and Müller glial reactivity. These phenotypes are similar to the ocular abnormalities observed in human patients suffering from Basal Cell Naevus Syndrome (BCNS), a disorder that has been linked to mutations in the human PTCH gene (the orthologue of the zebrafish ptc2), and point to the utility of the lep/ptc2 mutant line as a model for the study of BCNS-related ocular pathologies. Our findings regarding CMZ progenitor proliferation suggest that, in the zebrafish retina, Hh pathway activity may not affect cell cycle kinetics; rather, it likely regulates the size of the retinal progenitor pool in the CMZ. BioMed Central 2009-10-19 /pmc/articles/PMC2770046/ /pubmed/19840373 http://dx.doi.org/10.1186/1471-213X-9-52 Text en Copyright © 2009 Bibliowicz and Gross; licensee BioMed Central Ltd. http://creativecommons.org/licenses/by/2.0 This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( (http://creativecommons.org/licenses/by/2.0) ), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Research Article
Bibliowicz, Jonathan
Gross, Jeffrey M
Expanded progenitor populations, vitreo-retinal abnormalities, and Müller glial reactivity in the zebrafish leprechaun/patched2 retina
title Expanded progenitor populations, vitreo-retinal abnormalities, and Müller glial reactivity in the zebrafish leprechaun/patched2 retina
title_full Expanded progenitor populations, vitreo-retinal abnormalities, and Müller glial reactivity in the zebrafish leprechaun/patched2 retina
title_fullStr Expanded progenitor populations, vitreo-retinal abnormalities, and Müller glial reactivity in the zebrafish leprechaun/patched2 retina
title_full_unstemmed Expanded progenitor populations, vitreo-retinal abnormalities, and Müller glial reactivity in the zebrafish leprechaun/patched2 retina
title_short Expanded progenitor populations, vitreo-retinal abnormalities, and Müller glial reactivity in the zebrafish leprechaun/patched2 retina
title_sort expanded progenitor populations, vitreo-retinal abnormalities, and müller glial reactivity in the zebrafish leprechaun/patched2 retina
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2770046/
https://www.ncbi.nlm.nih.gov/pubmed/19840373
http://dx.doi.org/10.1186/1471-213X-9-52
work_keys_str_mv AT bibliowiczjonathan expandedprogenitorpopulationsvitreoretinalabnormalitiesandmullerglialreactivityinthezebrafishleprechaunpatched2retina
AT grossjeffreym expandedprogenitorpopulationsvitreoretinalabnormalitiesandmullerglialreactivityinthezebrafishleprechaunpatched2retina