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The Regulation of Notch Signaling in Retinal Development and Regeneration

  • Organ Development and Regeneration (D Shin and U Apte, Section Editors)
  • Published:
Current Pathobiology Reports

Abstract

Purpose of Review

Notch signaling is an important component of retinal progenitor cell maintenance and Muller glia (MG) specification during development, and its manipulation may be critical for allowing MG to re-enter the cell cycle and regenerate neurons in adults. In mammals, MG respond to retinal injury by undergoing a gliotic response rather than a regenerative one. Understanding the complexities of Notch signaling may allow for strategies that enhance regeneration over gliosis.

Recent Findings

Notch signaling is regulated at multiple levels and is interdependent with various other signaling pathways in both the receptor- and ligand-expressing cells. The precise spatial and temporal patterning of Notch components is necessary for proper retinal development. Regenerative species undergo a dynamic regulation of Notch signaling in MG upon injury, whereas non-regenerative species fail to productively regulate Notch.

Summary

Notch signaling is malleable, such that the altered composition of growth and transcription factors in the developing and mature retinas results in different Notch-mediated responses. Successful regeneration will require the manipulation of the retinal environment to foster a dynamic rather than static regulation of Notch signaling in concert with other reprogramming and differentiation factors.

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Funding

The authors were supported by the NIH (NEI grant RO1 EY 018132, Kirschstein-NRSA 4T32HD007505-20), a Research to Prevent Blindness Innovative Ophthalmic Research Award, and gifts from the Marjorie and Maxwell Jospey Foundation and Shirlye and Peter Helman Fund.

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  1. Molecular and Behavioral Neuroscience Institute, Department of Biological Chemistry, University of Michigan, 5045 BSRB, 109 Zina Pitcher PL, Ann Arbor, MI, 48109-2200, USA

    Elizabeth A. Mills & Daniel Goldman

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Correspondence to Daniel Goldman.

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Mills, E.A., Goldman, D. The Regulation of Notch Signaling in Retinal Development and Regeneration. Curr Pathobiol Rep 5, 323–331 (2017). https://doi.org/10.1007/s40139-017-0153-7

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