| Autor: |
Riveiro, Alba Redo, Mariani, Luca, Malmberg, Emily, Amendola, Pier Giorgio, Peltonen, Juhani, Wong, Garry, Salcini, Anna Elisabetta |
| Předmět: |
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| Zdroj: |
Development (09501991); 2017, Vol. 144 Issue 5, p856-565, 10p |
| Abstrakt: |
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. [ABSTRACT FROM AUTHOR] |
| Databáze: |
Complementary Index |
| Externí odkaz: |
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