RRC ID 48830
Author Riveiro AR, Mariani L, Malmberg E, Amendola PG, Peltonen J, Wong G, Salcini AE.
Title JMJD-1.2/PHF8 controls axon guidance by regulating Hedgehog-like signaling.
Journal Development
Abstract 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.
Volume 144(5)
Pages 856-865
Published 2017-3-1
DOI 10.1242/dev.142695
PII dev.142695
PMID 28126843
MeSH Actins / metabolism Animals Animals, Genetically Modified Axon Guidance* Axons / metabolism* CRISPR-Cas Systems Caenorhabditis elegans / metabolism* Caenorhabditis elegans Proteins / metabolism* Disease Models, Animal Epigenesis, Genetic Gene Expression Regulation, Developmental* Hedgehog Proteins / metabolism* Histone Demethylases / metabolism Jumonji Domain-Containing Histone Demethylases / metabolism* Neurons / metabolism RNA Interference Signal Transduction
IF 5.611
Times Cited 7
C.elegans tm3713