Human Molecular Genetics Advance Access first published online on November 5, 2009
This version [Corrected Proof] published online on November 11, 2009
Human Molecular Genetics, doi:10.1093/hmg/ddp500
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The nystagmus-associated FRMD7 gene regulates neuronal outgrowth and development
1 MRC Toxicology Unit, University of Leicester, Leicester LE1 9HN, UK, 2 MRC-Wellcome Trust Human Developmental Biology Resource (Newcastle), Institute of Human Genetics, Newcastle University, International Centre for Life, Newcastle upon Tyne NE1 3BZ, UK, 3 Ophthalmology Group, University of Leicester, Leicester LE2 7LX, UK and 4 German Centre for Neurodegenerative Diseases (DZNE), Ludwig-Erhard-Allee 2, 53175 Bonn, Germany
* To whom correspondence should be addressed. Tel: +49 228308990; Fax: +49 228308990; Email: pierluigi.nicotera{at}dzne.de
Received September 10, 2009; Accepted October 26, 2009
Mutations in the gene encoding FERM domain-containing 7 protein (FRMD7) are recognized as an important cause of X-linked idiopathic infantile nystagmus (IIN). However, the precise role of FRMD7 and its involvement in the pathogenesis of IIN are not understood. In the present study, we have explored the role of FRMD7 in neuronal development. Using in situ hybridization and immunohistochemistry, we reveal that FRMD7 expression is spatially and temporally regulated in both the human and mouse brain during embryonic and fetal development. Furthermore, we show that FRMD7 expression is up-regulated upon retinoic acid (RA)-induced differentiation of mouse neuroblastoma NEURO2A cells, suggesting FRMD7 may play a role in this process. Indeed, we demonstrate, for the first time, that knockdown of FRMD7 during neuronal differentiation results in altered neurite development. Taken together, our data suggest that FRMD7 is involved in multiple aspects of neuronal development, and have direct importance to further understanding the pathogenesis of IIN.
The authors wish it to be known that, in their opinion, the first two authors should be regarded as joint First Authors.