title: Substituting mouse transcription factor Pou4f2 with a sea urchin orthologue restores retinal ganglion cell development.
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.
authors.affiliation: Department of Systems Biology, Unit 0950, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
authors.forename: Chai-An
authors.identifier: http://orcid.org/0000-0002-9700-6964
authors.initials: CA
authors.lastname: Mao
authors.affiliation: Department of Systems Biology, Unit 0950, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
authors.forename: Cavit
authors.identifier: http://orcid.org/0000-0001-8472-7052
authors.initials: C
authors.lastname: Agca
authors.affiliation: College of Optometry, University of Houston, Houston, TX 77204, USA.
authors.forename: Julie A
authors.initials: JA
authors.lastname: Mocko-Strand
authors.affiliation: College of Optometry, University of Houston, Houston, TX 77204, USA.
authors.forename: Jing
authors.initials: J
authors.lastname: Wang
authors.affiliation: Museum für Naturkunde, Berlin 10115, Germany.
authors.forename: Esther
authors.initials: E
authors.lastname: Ullrich-Lüter
authors.affiliation: Department of Systems Biology, Unit 0950, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
authors.forename: Ping
authors.initials: P
authors.lastname: Pan
authors.affiliation: Department of Systems Biology, Unit 0950, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
authors.forename: Steven W
authors.initials: SW
authors.lastname: Wang
authors.affiliation: Biology and Evolution of Marine Organisms, Stazione Zoologica Anton Dohrn, Naples 80121, Italy.
authors.forename: Maria Ina
authors.initials: MI
authors.lastname: Arnone
authors.affiliation: College of Optometry, University of Houston, Houston, TX 77204, USA.
authors.forename: Laura J
authors.initials: LJ
authors.lastname: Frishman
authors.affiliation: Department of Systems Biology, Unit 0950, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA whklein@mdanderson.org.
authors.forename: William H
authors.initials: WH
authors.lastname: Klein
mesh_terms: D000818:Animals; D004622:Embryo, Mammalian / Q000196:embryology; D004625:Embryo, Nonmammalian / Q000196:embryology; D018507:Gene Expression Regulation, Developmental; D018398:Homeodomain Proteins / Q000235:genetics* / Q000378:metabolism; D051379:Mice / Q000235:genetics* / Q000254:growth & development / Q000378:metabolism; D012165:Retinal Ganglion Cells / Q000166:cytology / Q000378:metabolism*; D047270:Strongylocentrotus purpuratus / Q000235:genetics* / Q000378:metabolism; D050820:Transcription Factor Brn-3B / Q000235:genetics* / Q000378:metabolism
chemical_list: D018398:Homeodomain Proteins; C085559:Pou4f2 protein, mouse; D050820:Transcription Factor Brn-3B
keywords: Pou4f2/Brn3b; echinoderm photoreceptors; retinal development; retinal ganglion cells; transcription factor evolution