July 2018
Volume 59, Issue 9
Open Access
ARVO Annual Meeting Abstract  |   July 2018
Pivotal roles of Fezf2 in differentiation of cone OFF bipolar cells and functional maturation of cone ON bipolar cells in developing mouse retina
Author Affiliations & Notes
  • Sumiko Watanabe
    Molecular & Developmental Biol, Univ of Tokyo, Inst Med Science, Tokyo, TOKYO, Japan
  • Atsushi Mizota
    Department of Ophthalmology, Teikyo University School of Medicine , Tokyo, Japan
  • Haruna Suzuki
    Molecular & Developmental Biol, Univ of Tokyo, Inst Med Science, Tokyo, TOKYO, Japan
  • Footnotes
    Commercial Relationships   Sumiko Watanabe, None; Atsushi Mizota, None; Haruna Suzuki, None
  • Footnotes
    Support  grant-in-aid from the Ministry of Education, Culture, Sports, Science, and Technology of Japan (15H04695 )
Investigative Ophthalmology & Visual Science July 2018, Vol.59, 591. doi:https://doi.org/
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      Sumiko Watanabe, Atsushi Mizota, Haruna Suzuki; Pivotal roles of Fezf2 in differentiation of cone OFF bipolar cells and functional maturation of cone ON bipolar cells in developing mouse retina. Invest. Ophthalmol. Vis. Sci. 2018;59(9):591. doi: https://doi.org/.

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      © ARVO (1962-2015); The Authors (2016-present)

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Abstract

Purpose : During development, multipotent retinal progenitors differentiate into several classes of neurons and Müller glia, that are generated in a specific temporal order. A number of transcription factors are key regulators of the initial commitment of retinal progenitors to a neuronal type and their maturation. Here, we have investigated the expression and function of Fezf2, Fez zinc finger family of transcription factor, in the developing mouse retina.

Methods : Expression of Fezf2 was examined by RT-qPCR and in situ hybridization. Protein expression pattern was examined by mouse having beta-galactosidase in Fezf2 locus. Function of Fezf2 in retinal development was examined by Fezf2 knock-out mice by immunohistochemistry of sectioned retinas, and the electron microscopic analysis. Retinal functional analysis of the mice was done by electroretinogram.

Results : Expression of Fezf2 was strongly observed in the embryonic retinal progenitors at E14 and declined quickly in subsequent development of retina. Then, in postnatal stage at around post natal day 8, Fezf2 was transiently expressed then declined again. Analyses of mice in which Fezf2 coding region was substituted with b-D-galactosidase showed that Fezf2 is expressed in a subset of cone OFF bipolar cells and required for their differentiation. Using electroretinogram, we found that Fezf2 knockout retina exhibited significantly reduced photopic b-wave, suggesting functional abnormality of cone ON bipolar cells. Furthermore, reduced expression of synaptic protein Trpm1 and structural alteration of ON bipolar cell invagination, both of which affected cone photoreceptor terminal synaptic activity, was identified by transmission electron microscopy and immunohistochemistry, respectively.

Conclusions : Our results show that Fezf2 is indispensable in differentiation of bipolar precursors into cone OFF bipolar cells and in functional maturation of cone ON bipolar cells during development of mouse retina. These results contribute to our understanding of how diversity of neuronal subtypes and hence specificity of neuronal connections are established in the retina by intrinsic cues.

This is an abstract that was submitted for the 2018 ARVO Annual Meeting, held in Honolulu, Hawaii, April 29 - May 3, 2018.

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