The LIM-homeobox transcription factor Isl1 plays crucial roles in the development of multiple arcuate nucleus neurons.
Development
; 143(20): 3763-3773, 2016 10 15.
Article
en En
| MEDLINE
| ID: mdl-27578785
ABSTRACT
Neurons in the hypothalamic arcuate nucleus relay and translate important cues from the periphery into the central nervous system. However, the gene regulatory program directing their development remains poorly understood. Here, we report that the LIM-homeodomain transcription factor Isl1 is expressed in several subpopulations of developing arcuate neurons and plays crucial roles in their fate specification. Mice with conditional deletion of the Isl1 gene in developing hypothalamus display severe deficits in both feeding and linear growth. Consistent with these results, their arcuate nucleus fails to express key fate markers of Isl1-expressing neurons that regulate feeding and growth. These include the orexigenic neuropeptides AgRP and NPY for specifying AgRP-neurons, the anorexigenic neuropeptide αMSH for POMC-neurons, and two growth-stimulatory peptides, growth hormone-releasing hormone (GHRH) for GHRH-neurons and somatostatin (Sst) for Sst-neurons. Finally, we show that Isl1 directly enhances the expression of AgRP by cooperating with the key orexigenic transcription factors glucocorticoid receptor and brain-specific homeobox factor. Our results identify Isl1 as a crucial transcription factor that plays essential roles in the gene regulatory program directing development of multiple arcuate neuronal subpopulations.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Factores de Transcripción
/
Núcleo Arqueado del Hipotálamo
/
Proteínas con Homeodominio LIM
Tipo de estudio:
Prognostic_studies
Límite:
Animals
/
Female
/
Humans
/
Pregnancy
Idioma:
En
Revista:
Development
Asunto de la revista:
BIOLOGIA
/
EMBRIOLOGIA
Año:
2016
Tipo del documento:
Article
País de afiliación:
Estados Unidos