Substituting mouse transcription factor Pou4f2 with a sea urchin orthologue restores retinal ganglion cell development

Author:

Mao Chai-An1ORCID,Agca Cavit1ORCID,Mocko-Strand Julie A.2,Wang Jing2,Ullrich-Lüter Esther3,Pan Ping1,Wang Steven W.1,Arnone Maria Ina4,Frishman Laura J.2,Klein William H.1

Affiliation:

1. Department of Systems Biology, Unit 0950, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA

2. College of Optometry, University of Houston, Houston, TX 77204, USA

3. Museum für Naturkunde, Berlin 10115, Germany

4. Biology and Evolution of Marine Organisms, Stazione Zoologica Anton Dohrn, Naples 80121, Italy

Abstract

Pou domain transcription factor Pou4f2 is essential for the development of retinal ganglion cells (RGCs) in the vertebrate retina. A distant orthologue of Pou4f2 exists in the genome of the sea urchin (class Echinoidea) Strongylocentrotus purpuratus ( SpPou4f1/2 ), yet the photosensory structure of sea urchins is strikingly different from that of the mammalian retina. Sea urchins have no obvious eyes, but have photoreceptors clustered around their tube feet disc. The mechanisms that are associated with the development and function of photoreception in sea urchins are largely unexplored. As an initial approach to better understand the sea urchin photosensory structure and relate it to the mammalian retina, we asked whether SpPou4f1/2 could support RGC development in the absence of Pou4f2 . To answer this question, we replaced genomic Pou4f2 with an SpPou4f1/2 cDNA. In Pou4f2 -null mice, retinas expressing SpPou4f1/2 were outwardly identical to those of wild-type mice. SpPou4f1/2 retinas exhibited dark-adapted electroretinogram scotopic threshold responses, indicating functionally active RGCs. During retinal development, SpPou4f1/2 activated RGC-specific genes and in S. purpuratus , SpPou4f2 was expressed in photoreceptor cells of tube feet in a pattern distinct from Opsin4 and Pax6. Our results suggest that SpPou4f1/2 and Pou4f2 share conserved components of a gene network for photosensory development and they maintain their conserved intrinsic functions despite vast morphological differences in mouse and sea urchin photosensory structures.

Funder

Velux Foundation

National Cancer Institute

Welch Foundation

National Eye Institute

Publisher

The Royal Society

Subject

General Agricultural and Biological Sciences,General Environmental Science,General Immunology and Microbiology,General Biochemistry, Genetics and Molecular Biology,General Medicine

Reference34 articles.

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