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Lmx1b is required at multiple stages to build expansive serotonergic axon architectures
Formation of long-range axons occurs over multiple stages of morphological maturation. However, the intrinsic transcriptional mechanisms that temporally control different stages of axon projection development are unknown. Here, we addressed this question by studying the formation of mouse serotonin...
Autores principales: | , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
eLife Sciences Publications, Ltd
2019
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6685705/ https://www.ncbi.nlm.nih.gov/pubmed/31355748 http://dx.doi.org/10.7554/eLife.48788 |
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author | Donovan, Lauren J Spencer, William C Kitt, Meagan M Eastman, Brent A Lobur, Katherine J Jiao, Kexin Silver, Jerry Deneris, Evan S |
author_facet | Donovan, Lauren J Spencer, William C Kitt, Meagan M Eastman, Brent A Lobur, Katherine J Jiao, Kexin Silver, Jerry Deneris, Evan S |
author_sort | Donovan, Lauren J |
collection | PubMed |
description | Formation of long-range axons occurs over multiple stages of morphological maturation. However, the intrinsic transcriptional mechanisms that temporally control different stages of axon projection development are unknown. Here, we addressed this question by studying the formation of mouse serotonin (5-HT) axons, the exemplar of long-range profusely arborized axon architectures. We report that LIM homeodomain factor 1b (Lmx1b)-deficient 5-HT neurons fail to generate axonal projections to the forebrain and spinal cord. Stage-specific targeting demonstrates that Lmx1b is required at successive stages to control 5-HT axon primary outgrowth, selective routing, and terminal arborization. We show a Lmx1b→Pet1 regulatory cascade is temporally required for 5-HT arborization and upregulation of the 5-HT axon arborization gene, Protocadherin-alphac2, during postnatal development of forebrain 5-HT axons. Our findings identify a temporal regulatory mechanism in which a single continuously expressed transcription factor functions at successive stages to orchestrate the progressive development of long-range axon architectures enabling expansive neuromodulation. |
format | Online Article Text |
id | pubmed-6685705 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | eLife Sciences Publications, Ltd |
record_format | MEDLINE/PubMed |
spelling | pubmed-66857052019-08-09 Lmx1b is required at multiple stages to build expansive serotonergic axon architectures Donovan, Lauren J Spencer, William C Kitt, Meagan M Eastman, Brent A Lobur, Katherine J Jiao, Kexin Silver, Jerry Deneris, Evan S eLife Developmental Biology Formation of long-range axons occurs over multiple stages of morphological maturation. However, the intrinsic transcriptional mechanisms that temporally control different stages of axon projection development are unknown. Here, we addressed this question by studying the formation of mouse serotonin (5-HT) axons, the exemplar of long-range profusely arborized axon architectures. We report that LIM homeodomain factor 1b (Lmx1b)-deficient 5-HT neurons fail to generate axonal projections to the forebrain and spinal cord. Stage-specific targeting demonstrates that Lmx1b is required at successive stages to control 5-HT axon primary outgrowth, selective routing, and terminal arborization. We show a Lmx1b→Pet1 regulatory cascade is temporally required for 5-HT arborization and upregulation of the 5-HT axon arborization gene, Protocadherin-alphac2, during postnatal development of forebrain 5-HT axons. Our findings identify a temporal regulatory mechanism in which a single continuously expressed transcription factor functions at successive stages to orchestrate the progressive development of long-range axon architectures enabling expansive neuromodulation. eLife Sciences Publications, Ltd 2019-07-29 /pmc/articles/PMC6685705/ /pubmed/31355748 http://dx.doi.org/10.7554/eLife.48788 Text en © 2019, Donovan et al http://creativecommons.org/licenses/by/4.0/ http://creativecommons.org/licenses/by/4.0/This article is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use and redistribution provided that the original author and source are credited. |
spellingShingle | Developmental Biology Donovan, Lauren J Spencer, William C Kitt, Meagan M Eastman, Brent A Lobur, Katherine J Jiao, Kexin Silver, Jerry Deneris, Evan S Lmx1b is required at multiple stages to build expansive serotonergic axon architectures |
title | Lmx1b is required at multiple stages to build expansive serotonergic axon architectures |
title_full | Lmx1b is required at multiple stages to build expansive serotonergic axon architectures |
title_fullStr | Lmx1b is required at multiple stages to build expansive serotonergic axon architectures |
title_full_unstemmed | Lmx1b is required at multiple stages to build expansive serotonergic axon architectures |
title_short | Lmx1b is required at multiple stages to build expansive serotonergic axon architectures |
title_sort | lmx1b is required at multiple stages to build expansive serotonergic axon architectures |
topic | Developmental Biology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6685705/ https://www.ncbi.nlm.nih.gov/pubmed/31355748 http://dx.doi.org/10.7554/eLife.48788 |
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