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Huntingtin interacting protein 1 can regulate neurogenesis in Drosophila
Author(s) -
Moores Justin N.,
Roy Sophie,
Nicholson Donald W.,
Staveley Brian E.
Publication year - 2008
Publication title -
european journal of neuroscience
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.346
H-Index - 206
eISSN - 1460-9568
pISSN - 0953-816X
DOI - 10.1111/j.1460-9568.2008.06359.x
Subject(s) - notch signaling pathway , neurogenesis , huntingtin , biology , microbiology and biotechnology , signal transduction , cell fate determination , notch proteins , hes3 signaling axis , hairless , genetics , gene , transcription factor , mutant
Huntington’s disease (HD) is associated with a range of cellular consequences including selective neuronal death and decreased levels of neurogenesis. Ultimately, these altered processes are dependent upon proteins that interact with Huntingtin (Htt) such as the Huntingtin‐interacting protein 1 (Hip1) which has a reduced binding preference to expanded Htt. These effects are similar to those observed with modified Notch signal transduction. As Hip1 plays a key role in endocytosis and intracellular transport, and activation of the Notch signal requires both, we investigated putative links between Hip1 and Notch signaling in flies. We have identified two forms of Hip1 that may be produced through the use of alternative first exons: a version of Hip1 with a lipid‐binding ANTH domain and Hip1ΔANTH lacking this domain. The directed expression of Hip1 decreases, while expression of Hip1ΔANTH increases, the density of sensory microchaetae on the dorsal notum, a classical model of neurogenesis. A reduction in microchaetae density associated with Notch Microchaetae Deficient (MCD) ( N MCD ) alleles is sensitive to both Hip1 and Hip1ΔANTH levels, as are the bristle phenotypes generated by misexpression of deltex , a key mediator of Notch signaling. Genetic studies further demonstrate that the observed effects of Hip1 and of Hip1ΔANTH are sensitive to achaete gene dosage while insensitive to the levels of E(Spl) , suggesting a non‐canonical Notch neurogenic signal through a deltex‐ dependent pathway. The novel role we describe for Hip1 in Notch‐mediated neurogenesis provides a functional link between Notch signaling and proteins related to HD.