JMJD-1.2/PHF8 controls axon guidance by regulating hedgehoglike signaling
Riveiro A.R.1; Mariani L.1; Malmberg E.1; Amendola P.G.1; Peltonen J.2; Wong G.3; Salcini A.E.1
Source PublicationDevelopment (Cambridge)
ISSN14779129 09501991
AbstractComponents 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.
KeywordAxon guidance C. elegans Epigenetics Hedgehog signaling Histone demethylase Neuronal development
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Cited Times [WOS]:5   [WOS Record]     [Related Records in WOS]
Document TypeJournal article
CollectionUniversity of Macau
Affiliation1.Københavns Universitet
2.Itä-Suomen yliopisto
3.Universidade de Macau
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Riveiro A.R.,Mariani L.,Malmberg E.,et al. JMJD-1.2/PHF8 controls axon guidance by regulating hedgehoglike signaling[J]. Development (Cambridge),2017,144(5):856-865.
APA Riveiro A.R..,Mariani L..,Malmberg E..,Amendola P.G..,Peltonen J..,...&Salcini A.E..(2017).JMJD-1.2/PHF8 controls axon guidance by regulating hedgehoglike signaling.Development (Cambridge),144(5),856-865.
MLA Riveiro A.R.,et al."JMJD-1.2/PHF8 controls axon guidance by regulating hedgehoglike signaling".Development (Cambridge) 144.5(2017):856-865.
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