Nolz1 expression is required in dopaminergic axon guidance and striatal innervation

Clement Soleilhavoup; Marco Travaglio; Kieran Patrick; Pedro Garção; Elangovan Boobalan; Youri Adolfs; Ruth V Spriggs; Emma Moles-Garcia; Dalbir Dhiraj; Tony Oosterveen; Sarah L Ferri; Ted Abel; Edward S Brodkin; R Jeroen Pasterkamp; Brian P Brooks; Lia Panman

doi:10.1038/s41467-020-16947-6

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Nolz1 expression is required in dopaminergic axon guidance and striatal innervation

Journal article

Open access

Peer reviewed

Nolz1 expression is required in dopaminergic axon guidance and striatal innervation

Clement Soleilhavoup, Marco Travaglio, Kieran Patrick, Pedro Garção, Elangovan Boobalan, Youri Adolfs, Ruth V Spriggs, Emma Moles-Garcia, Dalbir Dhiraj, Tony Oosterveen, …

Nature communications, Vol.11(1), pp.3111-3111

06/19/2020

DOI: 10.1038/s41467-020-16947-6

PMCID: PMC7305235

PMID: 32561725

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Abstract

Midbrain dopaminergic (DA) axons make long longitudinal projections towards the striatum. Despite the importance of DA striatal innervation, processes involved in establishment of DA axonal connectivity remain largely unknown. Here we demonstrate a striatal-specific requirement of transcriptional regulator Nolz1 in establishing DA circuitry formation. DA projections are misguided and fail to innervate the striatum in both constitutive and striatal-specific Nolz1 mutant embryos. The lack of striatal Nolz1 expression results in nigral to pallidal lineage conversion of striatal projection neuron subtypes. This lineage switch alters the composition of secreted factors influencing DA axonal tract formation and renders the striatum non-permissive for dopaminergic and other forebrain tracts. Furthermore, transcriptomic analysis of wild-type and Nolz1 mutant striatal tissue led to the identification of several secreted factors that underlie the observed guidance defects and proteins that promote DA axonal outgrowth. Together, our data demonstrate the involvement of the striatum in orchestrating dopaminergic circuitry formation.

Microfluidic Analytical Techniques

Microinjections

Carbocyanines - administration & dosage

Embryo, Mammalian

Tissue Culture Techniques

Corpus Striatum - growth & development

Axons - physiology

Intracellular Signaling Peptides and Proteins - metabolism

Nerve Net - physiology

Nerve Tissue Proteins - genetics

Mice, Knockout

Nerve Tissue Proteins - metabolism

Microscopy, Confocal

Animals

Dopaminergic Neurons - physiology

Female

Fluorescent Dyes - administration & dosage

Axon Guidance - physiology

Corpus Striatum - diagnostic imaging

Intracellular Signaling Peptides and Proteins - genetics

Intravital Microscopy

Details

Title: Subtitle: Nolz1 expression is required in dopaminergic axon guidance and striatal innervation
Creators: Clement Soleilhavoup - MRC Toxicology Unit, University of Cambridge, Hodgkin Building, Lancaster Road, Leicester, LE1 9HN, UK
Marco Travaglio - MRC Toxicology Unit, University of Cambridge, Hodgkin Building, Lancaster Road, Leicester, LE1 9HN, UK
Kieran Patrick - MRC Toxicology Unit, University of Cambridge, Hodgkin Building, Lancaster Road, Leicester, LE1 9HN, UK
Pedro Garção - MRC Toxicology Unit, University of Cambridge, Hodgkin Building, Lancaster Road, Leicester, LE1 9HN, UK
Elangovan Boobalan - Ophthalmic Genetics & Visual Function Branch, National Eye Institute, National Institutes of Health, Bethesda, MD, 20892, USA
Youri Adolfs - Department of Translational Neuroscience, UMC Utrecht Brain Center, University Medical Center Utrecht, Utrecht University, 3584 CG, Utrecht, The Netherlands
Ruth V Spriggs - MRC Toxicology Unit, University of Cambridge, Hodgkin Building, Lancaster Road, Leicester, LE1 9HN, UK
Emma Moles-Garcia - MRC Toxicology Unit, University of Cambridge, Hodgkin Building, Lancaster Road, Leicester, LE1 9HN, UK
Dalbir Dhiraj - MRC Toxicology Unit, University of Cambridge, Hodgkin Building, Lancaster Road, Leicester, LE1 9HN, UK
Tony Oosterveen - MRC Toxicology Unit, University of Cambridge, Hodgkin Building, Lancaster Road, Leicester, LE1 9HN, UK
Sarah L Ferri - Department of Neuroscience and Pharmacology, Iowa Neuroscience Institute, University of Iowa, Iowa City, IA, 52242, USA
Ted Abel - Department of Neuroscience and Pharmacology, Iowa Neuroscience Institute, University of Iowa, Iowa City, IA, 52242, USA
Edward S Brodkin - Center for Neurobiology and Behavior, Department of Psychiatry, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, 19104-3403, USA
R Jeroen Pasterkamp - Department of Translational Neuroscience, UMC Utrecht Brain Center, University Medical Center Utrecht, Utrecht University, 3584 CG, Utrecht, The Netherlands
Brian P Brooks - Ophthalmic Genetics & Visual Function Branch, National Eye Institute, National Institutes of Health, Bethesda, MD, 20892, USA
Lia Panman - MRC Toxicology Unit, University of Cambridge, Hodgkin Building, Lancaster Road, Leicester, LE1 9HN, UK. liapanman1@gmail.com
Resource Type: Journal article
Publication Details: Nature communications, Vol.11(1), pp.3111-3111
DOI: 10.1038/s41467-020-16947-6
PMID: 32561725
PMCID: PMC7305235
NLM abbreviation: Nat Commun
ISSN: 2041-1723
eISSN: 2041-1723
Publisher: England
Grant note: P50 MH096891 / NIMH NIH HHS Medical Research Council K01 MH119540 / NIMH NIH HHS
Language: English
Date published: 06/19/2020
Academic Unit: Molecular Physiology and Biophysics; Psychiatry; Stead Family Department of Pediatrics; Psychological and Brain Sciences; Iowa Neuroscience Institute; Developmental and Behavioral Pediatrics; Neuroscience and Pharmacology; Biochemistry and Molecular Biology
Record Identifier: 9984070337602771

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