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Author Notes:

Correspondence should be addressed to Dr. Richard A. Baines, Faculty of Life Sciences, University of Manchester, Oxford Road, Manchester M13 9PT, United Kingdom., Richard.Baines@manchester.ac.uk

Author contributions: V.W., T.D.S., C.G., A.A.P., A.H.B., and R.A.B. designed research; V.W., T.D.S., and C.G. performed research; V.W., T.D.S., and C.G. analyzed data; V.W., T.D.S., C.G., A.A.P., A.H.B., and R.A.B. wrote the paper.

We thank members of the R.A.B. and A.A.P. groups for advice.

The authors declare no competing financial interests.

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Research Funding:

This work was supported by The Wellcome Trust (090798 to R.A.B.; 068055/092545 to A.H.B.) and a Herchel Smith Postdoctoral Research Fellowship to T.D.S., C.G. was supported by the Epilepsy Foundation of America. A.H.B. was supported by the Gurdon Institute from The Wellcome Trust (092096) and CRUK (C6946/A14492).

This project benefited from the Manchester Fly Facility, established by the University of Manchester and The Wellcome Trust (087742).

Keywords:

  • aCC
  • central nervous system
  • Drosophila
  • muscle
  • RP3
  • Shaker

The Transcription Factors Islet and Lim3 Combinatorially Regulate Ion Channel Gene Expression

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Journal Title:

Journal of Neuroscience Nursing

Volume:

Volume 34, Number 7

Publisher:

, Pages 2538-2543

Type of Work:

Article | Final Publisher PDF

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.

Copyright information:

© 2014 Wolfram et al.

This is an Open Access work distributed under the terms of the Creative Commons Attribution 3.0 Unported License (http://creativecommons.org/licenses/by/3.0/).

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