Prdm13 is required for Ebf3+ amacrine cell formation in the retina

Noah B. Goodson, Jhenya Nahreini, Grace Randazzo, Ana Uruena, Jane E. Johnson, Joseph A. Brzezinski

Research output: Contribution to journalArticle

7 Scopus citations

Abstract

Amacrine interneurons play a critical role in the processing of visual signals within the retina. They are highly diverse, representing 30 or more distinct subtypes. Little is known about how amacrine subtypes acquire their unique gene expression and morphological features. We characterized the gene expression pattern of the zinc-finger transcription factor Prdm13 in the mouse. Consistent with a developmental role, Prdm13 was expressed by Ptf1a+ amacrine and horizontal precursors. Over time, Prdm13 expression diverged from the transiently expressed Ptf1a and marked just a subset of amacrine cells in the adult retina. While heterogeneous, we show that most of these Prdm13+ amacrine cells express the transcription factor Ebf3 and the calcium binding protein calretinin. Loss of Prdm13 did not affect the number of amacrine cells formed during development. However, we observed a modest loss of amacrine cells and increased apoptosis that correlated with the onset timing of Ebf3 expression. Adult Prdm13 loss-of-function mice had 25% fewer amacrine cells, altered calretinin expression, and a lack of Ebf3+ amacrines. Forcing Prdm13 expression in retinal progenitor cells did not significantly increase amacrine cell formation, Ebf3 or calretinin expression, and appeared detrimental to the survival of photoreceptors. Our data show that Prdm13 is not required for amacrine fate as a class, but is essential for the formation of Ebf3+ amacrine cell subtypes. Rather than driving subtype identity, Prdm13 may act by restricting competing fate programs to maintain identity and survival.

Original languageEnglish (US)
JournalDevelopmental Biology
DOIs
StateAccepted/In press - Jan 1 2017

Keywords

  • Amacrine
  • Calretinin
  • Ebf3
  • Inner plexiform layer
  • Prdm13
  • Retinal development

ASJC Scopus subject areas

  • Molecular Biology
  • Developmental Biology
  • Cell Biology

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    Goodson, N. B., Nahreini, J., Randazzo, G., Uruena, A., Johnson, J. E., & Brzezinski, J. A. (Accepted/In press). Prdm13 is required for Ebf3+ amacrine cell formation in the retina. Developmental Biology. https://doi.org/10.1016/j.ydbio.2017.12.003