Extrinsic and intrinsic signals converge on the Runx1/CBFß transcription factor for nonpeptidergic nociceptor maturation.
Elife
; 4: e10874, 2015 Sep 29.
Article
en En
| MEDLINE
| ID: mdl-26418744
ABSTRACT
The generation of diverse neuronal subtypes involves specification of neural progenitors and, subsequently, postmitotic neuronal differentiation, a relatively poorly understood process. Here, we describe a mechanism whereby the neurotrophic factor NGF and the transcription factor Runx1 coordinate postmitotic differentiation of nonpeptidergic nociceptors, a major nociceptor subtype. We show that the integrity of a Runx1/CBFß holocomplex is crucial for NGF-dependent nonpeptidergic nociceptor maturation. NGF signals through the ERK/MAPK pathway to promote expression of Cbfb but not Runx1 prior to maturation of nonpeptidergic nociceptors. In contrast, transcriptional initiation of Runx1 in nonpeptidergic nociceptor precursors is dependent on the homeodomain transcription factor Islet1, which is largely dispensable for Cbfb expression. Thus, an NGF/TrkA-MAPK-CBFß pathway converges with Islet1-Runx1 signaling to promote Runx1/CBFß holocomplex formation and nonpeptidergic nociceptor maturation. Convergence of extrinsic and intrinsic signals to control heterodimeric transcription factor complex formation provides a robust mechanism for postmitotic neuronal subtype specification.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Nociceptores
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Diferenciación Celular
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Subunidad alfa 2 del Factor de Unión al Sitio Principal
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Subunidad beta del Factor de Unión al Sitio Principal
Límite:
Animals
Idioma:
En
Revista:
Elife
Año:
2015
Tipo del documento:
Article
País de afiliación:
Estados Unidos