Please use this identifier to cite or link to this item: http://hdl.handle.net/2440/55804
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Type: Journal article
Title: Selective neuronal requirement for Huntingtin in the developing zebrafish
Author: Henshall, T.
Tucker, B.
Lumsden, A.
Nornes, S.
Lardelli, M.
Richards, R.
Citation: Human Molecular Genetics, 2009; 18(24):4830-4842
Publisher: Oxford Univ Press
Issue Date: 2009
ISSN: 0964-6906
1460-2083
Statement of
Responsibility: 
Tanya L. Henshall, Ben Tucker, Amanda L. Lumsden, Svanhild Nornes, Michael T. Lardelli and Robert I. Richards
Abstract: Huntington's disease shares a common molecular basis with eight other neurodegenerative diseases, expansion of an existing polyglutamine tract. In each case, this repeat tract occurs within otherwise unrelated proteins. These proteins show widespread and overlapping patterns of expression in the brain and yet the diseases are distinguished by neurodegeneration in a specific subset of neurons that are most sensitive to the mutation. It has therefore been proposed that expansion of the polyglutamine region in these genes may result in perturbation of the normal function of the respective proteins, and that this perturbation in some way contributes to the neuronal specificity of these diseases. The normal functions of these proteins have therefore become a focus for investigation as potential pathogenic pathways. We have used synthetic antisense morpholinos to inhibit the translation of huntingtin mRNA during early zebrafish development and have previously reported the effects of huntingtin reduction on iron transport and homeostasis. Here we report an analysis of the effects of huntingtin loss-of-function on the developing nervous system, observing distinct defects in morphology of neuromasts, olfactory placode and branchial arches. The potential common origins of these defects were explored, revealing impaired formation of the anterior-most region of the neural plate as indicated by reduced pre-placodal and telencephalic gene expression with no effect on mid- or hindbrain formation. These investigations demonstrate a specific ‘rate-limiting’ role for huntingtin in formation of the telencephalon and the pre-placodal region, and differing levels of requirement for huntingtin function in specific nerve cell types.
Keywords: Cartilage; Telencephalon; Neural Crest; Animals; Zebrafish; Humans; Huntington Disease; Brain-Derived Neurotrophic Factor; Zebrafish Proteins; Nerve Tissue Proteins; Cell Differentiation; Neural Plate; Sensory Receptor Cells; Neurogenesis; Gene Knockdown Techniques
RMID: 0020092864
DOI: 10.1093/hmg/ddp455
Appears in Collections:Molecular and Biomedical Science publications

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