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The homeobox transcription factor Even-skipped regulates acquisition of electrical properties in Drosophila neurons
BACKGROUND: While developmental processes such as axon pathfinding and synapse formation have been characterized in detail, comparatively less is known of the intrinsic developmental mechanisms that regulate transcription of ion channel genes in embryonic neurons. Early decisions, including motoneur...
Autores principales: | , , , , |
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Formato: | Texto |
Lenguaje: | English |
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BioMed Central
2006
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1679800/ https://www.ncbi.nlm.nih.gov/pubmed/17147779 http://dx.doi.org/10.1186/1749-8104-1-3 |
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author | Pym, Edward CG Southall, Tony D Mee, Christopher J Brand, Andrea H Baines, Richard A |
author_facet | Pym, Edward CG Southall, Tony D Mee, Christopher J Brand, Andrea H Baines, Richard A |
author_sort | Pym, Edward CG |
collection | PubMed |
description | BACKGROUND: While developmental processes such as axon pathfinding and synapse formation have been characterized in detail, comparatively less is known of the intrinsic developmental mechanisms that regulate transcription of ion channel genes in embryonic neurons. Early decisions, including motoneuron axon targeting, are orchestrated by a cohort of transcription factors that act together in a combinatorial manner. These transcription factors include Even-skipped (Eve), islet and Lim3. The perdurance of these factors in late embryonic neurons is, however, indicative that they might also regulate additional aspects of neuron development, including the acquisition of electrical properties. RESULTS: To test the hypothesis that a combinatorial code transcription factor is also able to influence the acquisition of electrical properties in embryonic neurons we utilized the molecular genetics of Drosophila to manipulate the expression of Eve in identified motoneurons. We show that increasing expression of this transcription factor, in two Eve-positive motoneurons (aCC and RP2), is indeed sufficient to affect the electrical properties of these neurons in early first instar larvae. Specifically, we observed a decrease in both the fast K(+ )conductance (I(Kfast)) and amplitude of quantal cholinergic synaptic input. We used charybdotoxin to pharmacologically separate the individual components of I(Kfast )to show that increased Eve specifically down regulates the Slowpoke (a BK Ca(2+)-gated potassium channel), but not Shal, component of this current. Identification of target genes for Eve, using DNA adenine methyltransferase identification, revealed strong binding sites in slowpoke and nAcRα-96Aa (a nicotinic acetylcholine receptor subunit). Verification using real-time PCR shows that pan-neuronal expression of eve is sufficient to repress transcripts for both slo and nAcRα-96Aa. CONCLUSION: Taken together, our findings demonstrate, for the first time, that Eve is sufficient to regulate both voltage- and ligand-gated currents in motoneurons, extending its known repertoire of action beyond its already characterized role in axon guidance. Our data are also consistent with a common developmental program that utilizes a defined set of transcription factors to determine both morphological and functional neuronal properties. |
format | Text |
id | pubmed-1679800 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2006 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-16798002006-12-02 The homeobox transcription factor Even-skipped regulates acquisition of electrical properties in Drosophila neurons Pym, Edward CG Southall, Tony D Mee, Christopher J Brand, Andrea H Baines, Richard A Neural Develop Research Article BACKGROUND: While developmental processes such as axon pathfinding and synapse formation have been characterized in detail, comparatively less is known of the intrinsic developmental mechanisms that regulate transcription of ion channel genes in embryonic neurons. Early decisions, including motoneuron axon targeting, are orchestrated by a cohort of transcription factors that act together in a combinatorial manner. These transcription factors include Even-skipped (Eve), islet and Lim3. The perdurance of these factors in late embryonic neurons is, however, indicative that they might also regulate additional aspects of neuron development, including the acquisition of electrical properties. RESULTS: To test the hypothesis that a combinatorial code transcription factor is also able to influence the acquisition of electrical properties in embryonic neurons we utilized the molecular genetics of Drosophila to manipulate the expression of Eve in identified motoneurons. We show that increasing expression of this transcription factor, in two Eve-positive motoneurons (aCC and RP2), is indeed sufficient to affect the electrical properties of these neurons in early first instar larvae. Specifically, we observed a decrease in both the fast K(+ )conductance (I(Kfast)) and amplitude of quantal cholinergic synaptic input. We used charybdotoxin to pharmacologically separate the individual components of I(Kfast )to show that increased Eve specifically down regulates the Slowpoke (a BK Ca(2+)-gated potassium channel), but not Shal, component of this current. Identification of target genes for Eve, using DNA adenine methyltransferase identification, revealed strong binding sites in slowpoke and nAcRα-96Aa (a nicotinic acetylcholine receptor subunit). Verification using real-time PCR shows that pan-neuronal expression of eve is sufficient to repress transcripts for both slo and nAcRα-96Aa. CONCLUSION: Taken together, our findings demonstrate, for the first time, that Eve is sufficient to regulate both voltage- and ligand-gated currents in motoneurons, extending its known repertoire of action beyond its already characterized role in axon guidance. Our data are also consistent with a common developmental program that utilizes a defined set of transcription factors to determine both morphological and functional neuronal properties. BioMed Central 2006-11-16 /pmc/articles/PMC1679800/ /pubmed/17147779 http://dx.doi.org/10.1186/1749-8104-1-3 Text en Copyright © 2006 Pym et al.; licensee BioMed Central Ltd http://creativecommons.org/licenses/by/2.0 This is an open access article distributed under the terms of the Creative Commons Attribution License ( (http://creativecommons.org/licenses/by/2.0) ), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Research Article Pym, Edward CG Southall, Tony D Mee, Christopher J Brand, Andrea H Baines, Richard A The homeobox transcription factor Even-skipped regulates acquisition of electrical properties in Drosophila neurons |
title | The homeobox transcription factor Even-skipped regulates acquisition of electrical properties in Drosophila neurons |
title_full | The homeobox transcription factor Even-skipped regulates acquisition of electrical properties in Drosophila neurons |
title_fullStr | The homeobox transcription factor Even-skipped regulates acquisition of electrical properties in Drosophila neurons |
title_full_unstemmed | The homeobox transcription factor Even-skipped regulates acquisition of electrical properties in Drosophila neurons |
title_short | The homeobox transcription factor Even-skipped regulates acquisition of electrical properties in Drosophila neurons |
title_sort | homeobox transcription factor even-skipped regulates acquisition of electrical properties in drosophila neurons |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1679800/ https://www.ncbi.nlm.nih.gov/pubmed/17147779 http://dx.doi.org/10.1186/1749-8104-1-3 |
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