Functional and Evolutionary Diversification of Otx2 and Crx in Vertebrate Retinal Photoreceptor and Bipolar Cell Development.
Animals
Cell Differentiation
Cell Lineage
Cell Survival
Evolution, Molecular
Gene Dosage
Gene Expression Profiling
Genetic Loci
HEK293 Cells
Homeodomain Proteins
/ metabolism
Humans
Jaw
/ anatomy & histology
Mice, Inbred ICR
Multigene Family
Otx Transcription Factors
/ metabolism
Photoreceptor Cells, Vertebrate
/ metabolism
Retinal Bipolar Cells
/ metabolism
Retinal Rod Photoreceptor Cells
/ metabolism
Trans-Activators
/ metabolism
Vertebrates
/ genetics
Bipolar cell
Cell fate
Crx
Evolution
Lamprey
Lineage analysis
Neofunctionalization
Otx2
Photoreceptor
Retina
Journal
Cell reports
ISSN: 2211-1247
Titre abrégé: Cell Rep
Pays: United States
ID NLM: 101573691
Informations de publication
Date de publication:
21 01 2020
21 01 2020
Historique:
received:
28
05
2019
revised:
06
11
2019
accepted:
18
12
2019
entrez:
23
1
2020
pubmed:
23
1
2020
medline:
18
3
2021
Statut:
ppublish
Résumé
Otx family homeoproteins Otx2 and Crx are expressed in photoreceptor precursor cells and bind to the common DNA-binding consensus sequence, but these two proteins have distinct functions in retinal development. To examine the functional substitutability of Otx2 and Crx, we generate knockin mouse lines in which Crx is replaced by Otx2 and vice versa. We find that Otx2 and Crx cannot be substituted in photoreceptor development. Subsequently, we investigate the function of Otx2 in photoreceptor and bipolar cell development. High Otx2 levels induce photoreceptor cell fate but not bipolar cell fate, whereas reduced Otx2 expression impairs bipolar cell maturation and survival. Furthermore, we identify Otx2 and Crx in the lamprey genome by using synteny analysis, suggesting that the last common ancestor of vertebrates possesses both Otx2 and Crx. We find that the retinal Otx2 expression pattern is different between lampreys and mice, suggesting that neofunctionalization of Otx2 occurred in the jawed vertebrate lineage.
Identifiants
pubmed: 31968244
pii: S2211-1247(19)31729-2
doi: 10.1016/j.celrep.2019.12.072
pii:
doi:
Substances chimiques
Homeodomain Proteins
0
Otx Transcription Factors
0
Otx2 protein, mouse
0
Trans-Activators
0
cone rod homeobox protein
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
658-671.e5Informations de copyright
Copyright © 2019 The Author(s). Published by Elsevier Inc. All rights reserved.
Déclaration de conflit d'intérêts
Declaration of Interests The authors declare that they have no conflicts of interest.