JMJD-1.2/PHF8 controls axon guidance by regulating Hedgehog-like signaling.
Development
; 144(5): 856-865, 2017 03 01.
Article
en En
| MEDLINE
| ID: mdl-28126843
Components of the KDM7 family of histone demethylases are implicated in neuronal development and one member, PHF8, is often found to be mutated in cases of X-linked mental retardation. However, how PHF8 regulates neurodevelopmental processes and contributes to the disease is still largely unknown. Here, we show that the catalytic activity of a PHF8 homolog in Caenorhabditis elegans, JMJD-1.2, is required non-cell-autonomously for proper axon guidance. Loss of JMJD-1.2 dysregulates transcription of the Hedgehog-related genes wrt-8 and grl-16, the overexpression of which is sufficient to induce the axonal defects. Deficiency of either wrt-8 or grl-16, or reduced expression of homologs of genes promoting Hedgehog signaling, restores correct axon guidance in jmjd-1.2 mutants. Genetic and overexpression data indicate that Hedgehog-related genes act on axon guidance through actin remodelers. Thus, our study highlights a novel function of jmjd-1.2 in axon guidance that might be relevant for the onset of X-linked mental retardation and provides compelling evidence of a conserved function of the Hedgehog pathway in C. elegans axon migration.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Axones
/
Caenorhabditis elegans
/
Regulación del Desarrollo de la Expresión Génica
/
Proteínas de Caenorhabditis elegans
/
Proteínas Hedgehog
/
Histona Demetilasas con Dominio de Jumonji
/
Orientación del Axón
Tipo de estudio:
Guideline
Límite:
Animals
Idioma:
En
Revista:
Development
Asunto de la revista:
BIOLOGIA
/
EMBRIOLOGIA
Año:
2017
Tipo del documento:
Article
País de afiliación:
Dinamarca
Pais de publicación:
Reino Unido