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[P2.48]: Inverse relationship between CDKL5 and MYCN expression in neuroblastoma cell lines during differentiation
Author(s) -
Trazzi S.,
Valli E.,
Fuchs C.,
Bartesaghi R.,
Perini G.,
Ciani E.
Publication year - 2010
Publication title -
international journal of developmental neuroscience
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.761
H-Index - 88
eISSN - 1873-474X
pISSN - 0736-5748
DOI - 10.1016/j.ijdevneu.2010.07.178
Subject(s) - library science , bologna process , citation , higher education , political science , law , computer science
Eye movements in vertebrates depend on the co-ordinated action of six extraocular muscles which are innervated by three nerves. In patients with the human eye movement disorder Duane retraction syndrome (DRS), neuroimaging data shows a perturbation of normal axon guidance and branching events of the abducens and oculomotor nerves. Families with the DURS2 variant of DRS harbour mutations in the chimaerin-1 (CHN1) gene (Miyake et al., 2008); CHN1 encodes the signalling molecule 2-chimaerin, which mediates neuronal responses to axon guidance cues. We have previously shown that electroporation of forms of 2-chimaerin harbouring human mutations into the oculomotor nerve of the chick embryo leads to striking axon guidance defects (Miyake et al., 2008). The axon guidance cues which lie upstream of 2-chimaerin in the oculomotor system are currently unknown. We are using the chick and the zebrafish embryo to test the hypothesis that 2-chimaerin lies downstream of Semaphorin3APlexin signalling during oculomotor axon guidance. In vitro, we find that oculomotor neurons carrying 2-chimaerin gain-offunction mutations display enhanced growth cone collapse in response to Sema3A, whereas RNAi knockdown of 2-chimaerin abrogates such collapse. In vivo, constructs which block Sema3Amediated signalling or RNAi knockdown of 2-chimaerin lead to axon overbranching and overshooting phenotypes. These observations suggest that Sema3A-mediated repulsion is mediated by 2-chimaerin in the oculomotor system, and plays an important role in targeting axon projections to the extraocular muscles. We are currently electroporating plasmids to manipulate Sema-Plexin signalling and 2-chimaerin function simultaneously in order to demonstrate an interaction in vivo. In addition, we have used time-lapse movies in the zebrafish to map the development of the oculomotor system in an Islet-1-GFP line. The generation of fish lines harbouring 2-chimaerin mutant forms will then allow us to understand how abnormal axon guidance occurs in Duane syndrome. Reference: