Combined inactivation of RB and Hippo converts differentiating Drosophila photoreceptors into eye progenitor cells through derepression of homothorax.
Dev Cell
; 58(21): 2261-2274.e6, 2023 11 06.
Article
en En
| MEDLINE
| ID: mdl-37848027
ABSTRACT
The retinoblastoma (RB) and Hippo pathways interact to regulate cell proliferation and differentiation. However, the mechanism of interaction is not fully understood. Drosophila photoreceptors with inactivated RB and Hippo pathways specify normally but fail to maintain their neuronal identity and dedifferentiate. We performed single-cell RNA sequencing to elucidate the cause of dedifferentiation and to determine the fate of these cells. We find that dedifferentiated cells adopt a progenitor-like fate due to inappropriate activation of the retinal differentiation suppressor homothorax (hth) by Yki/Sd. This results in the activation of a distinct Yki/Hth transcriptional program, driving photoreceptor dedifferentiation. We show that Rbf physically interacts with Yki and, together with the GAGA factor, inhibits the hth expression. Thus, RB and Hippo pathways cooperate to maintain photoreceptor differentiation by preventing inappropriate expression of hth in differentiating photoreceptors. Our work highlights the importance of both RB and Hippo pathway activities for maintaining the state of terminal differentiation.
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Texto completo:
1
Bases de datos:
MEDLINE
Asunto principal:
Retinoblastoma
/
Neoplasias de la Retina
/
Proteínas de Drosophila
Límite:
Animals
Idioma:
En
Revista:
Dev Cell
Asunto de la revista:
EMBRIOLOGIA
Año:
2023
Tipo del documento:
Article
País de afiliación:
Estados Unidos