The transcription factors islet and lim3 combinatorially regulate ion channel gene expression

Verena Wolfram, Tony D. Southall, Cengiz Günay, Astrid A. Prinz, Andrea H. Brand, Richard A. Baines

    Research output: Contribution to journalArticlepeer-review

    Abstract

    Expression of appropriate ion channels is essential to allow developing neurons to form functional networks. Our previous studies have identified LIM-homeodomain (HD) transcription factors (TFs), expressed by developing neurons, that are specifically able to regulate ion channel gene expression. In this study, we use the technique of DNA adenine methyltransferase identification (DamID) to identify putative gene targets of four such TFs that are differentially expressed in Drosophila motoneurons. Analysis of targets for Islet (Isl), Lim3, Hb9, and Even-skipped (Eve) identifies both ion channel genes and genes predicted to regulate aspects of dendritic and axonal morphology. Significantly, some ion channel genes are bound by more than one TF, consistent with the possibility of combinatorial regulation. One such gene is Shaker (Sh), which encodes a voltage-dependent fast K+channel (Kv1.1). DamID reveals that Sh is bound by both Isl and Lim3. We used body wall muscle as a test tissue because in conditions of low Ca2+, the fast K+ current is carried solely by Sh channels (unlike neurons in which a second fast K+ current, Shal, also contributes). Ectopic expression of isl, but not Lim3, is sufficient to reduce both Sh transcript and Sh current level. By contrast, coexpression of both TFs is additive, resulting in a significantly greater reduction in both Sh transcript and current compared with isl expression alone. These observations provide evidence for combinatorial activity of Isl and Lim3 in regulating ion channel gene expression. © 2014 the authors.
    Original languageEnglish
    Pages (from-to)2538-2543
    Number of pages5
    JournalJournal of Neuroscience
    Volume34
    Issue number7
    DOIs
    Publication statusPublished - 2014

    Keywords

    • aCC
    • Central nervous system
    • Drosophila
    • Muscle
    • RP3
    • Shaker

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