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

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^*

^*Corresponding author for this work

Research output: Contribution to journal › Article › Academic › peer-review

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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.

Original language	English
Article number	3111
Pages (from-to)	1-17
Journal	Nature Communications
Volume	11
Issue number	1
DOIs	https://doi.org/10.1038/s41467-020-16947-6
Publication status	Published - 19 Jun 2020

Keywords

Animals
Axon Guidance/physiology
Axons/physiology
Carbocyanines/administration & dosage
Corpus Striatum/diagnostic imaging
Dopaminergic Neurons/physiology
Embryo, Mammalian
Female
Fluorescent Dyes/administration & dosage
Intracellular Signaling Peptides and Proteins/genetics
Intravital Microscopy
Mice, Knockout
Microfluidic Analytical Techniques
Microinjections
Microscopy, Confocal
Nerve Net/physiology
Nerve Tissue Proteins/genetics
Tissue Culture Techniques

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Soleilhavoup, C., Travaglio, M., Patrick, K., Garção, P., Boobalan, E., Adolfs, Y., Spriggs, R. V., Moles-Garcia, E., Dhiraj, D., Oosterveen, T., Ferri, S. L., Abel, T., Brodkin, E. S., Pasterkamp, R. J., Brooks, B. P., & Panman, L. (2020). Nolz1 expression is required in dopaminergic axon guidance and striatal innervation. Nature Communications, 11(1), 1-17. Article 3111. https://doi.org/10.1038/s41467-020-16947-6

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title = "Nolz1 expression is required in dopaminergic axon guidance and striatal innervation",

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.",

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author = "Clement Soleilhavoup and Marco Travaglio and Kieran Patrick and Pedro Gar{\c c}{\~a}o and Elangovan Boobalan and Youri Adolfs and Spriggs, {Ruth V.} and Emma Moles-Garcia and Dalbir Dhiraj and Tony Oosterveen and Ferri, {Sarah L.} and Ted Abel and Brodkin, {Edward S.} and Pasterkamp, {R. Jeroen} and Brooks, {Brian P.} and Lia Panman",

year = "2020",

month = jun,

day = "19",

doi = "10.1038/s41467-020-16947-6",

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Soleilhavoup, C, Travaglio, M, Patrick, K, Garção, P, Boobalan, E, Adolfs, Y, Spriggs, RV, Moles-Garcia, E, Dhiraj, D, Oosterveen, T, Ferri, SL, Abel, T, Brodkin, ES, Pasterkamp, RJ, Brooks, BP & Panman, L 2020, 'Nolz1 expression is required in dopaminergic axon guidance and striatal innervation', Nature Communications, vol. 11, no. 1, 3111, pp. 1-17. https://doi.org/10.1038/s41467-020-16947-6

TY - JOUR

T1 - Nolz1 expression is required in dopaminergic axon guidance and striatal innervation

AU - Soleilhavoup, Clement

AU - Travaglio, Marco

AU - Patrick, Kieran

AU - Garção, Pedro

AU - Boobalan, Elangovan

AU - Adolfs, Youri

AU - Spriggs, Ruth V.

AU - Moles-Garcia, Emma

AU - Dhiraj, Dalbir

AU - Oosterveen, Tony

AU - Ferri, Sarah L.

AU - Abel, Ted

AU - Brodkin, Edward S.

AU - Pasterkamp, R. Jeroen

AU - Brooks, Brian P.

AU - Panman, Lia

PY - 2020/6/19

Y1 - 2020/6/19

N2 - 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.

AB - 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.

KW - Animals

KW - Axon Guidance/physiology

KW - Axons/physiology

KW - Carbocyanines/administration & dosage

KW - Corpus Striatum/diagnostic imaging

KW - Dopaminergic Neurons/physiology

KW - Embryo, Mammalian

KW - Female

KW - Fluorescent Dyes/administration & dosage

KW - Intracellular Signaling Peptides and Proteins/genetics

KW - Intravital Microscopy

KW - Mice, Knockout

KW - Microfluidic Analytical Techniques

KW - Microinjections

KW - Microscopy, Confocal

KW - Nerve Net/physiology

KW - Nerve Tissue Proteins/genetics

KW - Tissue Culture Techniques

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U2 - 10.1038/s41467-020-16947-6

DO - 10.1038/s41467-020-16947-6

M3 - Article

C2 - 32561725

AN - SCOPUS:85086631428

SN - 2041-1723

VL - 11

SP - 1

EP - 17

JO - Nature Communications

JF - Nature Communications

IS - 1

M1 - 3111

ER -

Nolz1 expression is required in dopaminergic axon guidance and striatal innervation

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