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...

Full description

Saved in:
Bibliographic Details
Published in:eLife 2019-07, Vol.8
Main Authors: Donovan, Lauren J, Spencer, William C, Kitt, Meagan M, Eastman, Brent A, Lobur, Katherine J, Jiao, Kexin, Silver, Jerry, Deneris, Evan S
Format: Article
Language:English
Subjects:
Animals
arborization
Axon guidance
Axonogenesis
Axons
Axons - physiology
Brain
development
Developmental Biology
Forebrain
Gene Expression Profiling
Genes
Homeobox
LIM-Homeodomain Proteins - deficiency
LIM-Homeodomain Proteins - metabolism
Lmx1b
Mice
Morphology
Neurogenesis
Neuromodulation
Neurons
Neuroscience
Phenols (Class of compounds)
Physiological aspects
Prosencephalon - cytology
Protocadherin
Serotonergic Neurons - physiology
Serotonin
Spinal cord
Spinal Cord - cytology
Statistical analysis
transcription factor
Transcription Factors - deficiency
Transcription Factors - metabolism
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary: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.
ISSN:2050-084X
2050-084X
DOI:10.7554/elife.48788