Pou2f1 and Pou2f2 cooperate to control the timing of cone photoreceptor production in the developing mouse retina.
Development
; 147(18)2020 09 28.
Article
en En
| MEDLINE
| ID: mdl-32878923
ABSTRACT
Multipotent retinal progenitor cells (RPCs) generate various cell types in a precise chronological order, but how exactly cone photoreceptor production is restricted to early stages remains unclear. Here, we show that the POU-homeodomain factors Pou2f1/Pou2f2, the homologs of Drosophila temporal identity factors nub/pdm2, regulate the timely production of cones in mice. Forcing sustained expression of Pou2f1 or Pou2f2 in RPCs expands the period of cone production, whereas misexpression in late-stage RPCs triggers ectopic cone production at the expense of late-born fates. Mechanistically, we report that Pou2f1 induces Pou2f2 expression, which binds to a POU motif in the promoter of the rod-inducing factor Nrl to repress its expression. Conversely, conditional inactivation of Pou2f2 in RPCs increases Nrl expression and reduces cone production. Finally, we provide evidence that Pou2f1 is part of a cross-regulatory cascade with the other temporal identity factors Ikzf1 and Casz1. These results uncover Pou2f1/2 as regulators of the temporal window for cone genesis and, given their widespread expression in the nervous system, raise the possibility of a general role in temporal patterning.This article has an associated 'The people behind the papers' interview.
Palabras clave
Texto completo:
1
Banco de datos:
MEDLINE
Asunto principal:
Retina
/
Células Fotorreceptoras Retinianas Conos
/
Factor 1 de Transcripción de Unión a Octámeros
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Factor 2 de Transcripción de Unión a Octámeros
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Proteínas del Ojo
Límite:
Animals
Idioma:
En
Revista:
Development
Asunto de la revista:
BIOLOGIA
/
EMBRIOLOGIA
Año:
2020
Tipo del documento:
Article
País de afiliación:
Canadá