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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...

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Autores principales: Donovan, Lauren J, Spencer, William C, Kitt, Meagan M, Eastman, Brent A, Lobur, Katherine J, Jiao, Kexin, Silver, Jerry, Deneris, Evan S
Formato: Online Artículo Texto
Lenguaje:English
Publicado: eLife Sciences Publications, Ltd 2019
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.
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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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