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[P238]: Loss of heparan sulphate‐6‐sulphotransferase 1 results in retinal ganglion cell axon guidance errors at the optic chiasm and dorsal thalamus of the developing mouse visual system
Author(s) -
Conway C.,
Pratt T.,
Price D.,
Mason J.
Publication year - 2006
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.2006.09.297
Subject(s) - optic chiasm , dorsum , citation , neuroscience , axon , library science , computer science , anatomy , biology , optic nerve
The tip, or growth cone, of an axon detects signalling cues in its extracellular environment and guides the growth of the axon to its destination. This behaviour requires protein synthesis in the axon and growth cone using locally stored mRNAs (Campbell and Holt, 2001). For example, the small GTPase RhoA is locally translated, causing Sema3A-mediated growth cone collapse. The RhoA mRNA is found in a punctate pattern along the axon and its 3UTR is both necessary and sufficient for transport of the mRNA along the axon to the growth cone (Wu et al., 2005). We have therefore searched for other, similar mRNAs in axons. We have cloned and sequenced a set of mRNAs from isolated axons. Axons were grown by culturing thalamic sections from E14.5 mouse embryos and then severed from the explant. The RNA was purified from the axons and amplified with RT-PCR. Twenty-three mRNAs were identified, including beta-catenin, another small GTPase RalA and beta-actin. In addition to its well-known role in Wnt signalling, betacatenin is also involved in N-cadherin-mediated cell adhesion behaviour. Beta-catenin connects N-cadherin to alpha-catenin and the actin cytoskeleten. This behaviour is inhibited by the signalling cue Slit via its receptor Robo, which tyrosine phosphorylates beta-catenin causing it to dissociate from the N-cadherin complex (Rhee et al., 2002). It is unclear whether or how locally synthesised beta-catenin is involved in this behaviour. We are now working to localise beta-catenin mRNA in axons and growth cones using in situ hybridisation (Wu et al., 2005). We are also looking for potential regulatory regions in our set of mRNAs, focussing in particular on the 3UTR and examining conservation and homology across different species. We hope this work will broaden our understanding of mRNAs in axons and growth cones and their involvement in axon guidance behaviour.