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 and Lia Panman ()
Additional contact information
Clement Soleilhavoup: University of Cambridge, Hodgkin Building
Marco Travaglio: University of Cambridge, Hodgkin Building
Kieran Patrick: University of Cambridge, Hodgkin Building
Pedro Garção: University of Cambridge, Hodgkin Building
Elangovan Boobalan: National Eye Institute, National Institutes of Health
Youri Adolfs: University Medical Center Utrecht, Utrecht University
Ruth V. Spriggs: University of Cambridge, Hodgkin Building
Emma Moles-Garcia: University of Cambridge, Hodgkin Building
Dalbir Dhiraj: University of Cambridge, Hodgkin Building
Tony Oosterveen: University of Cambridge, Hodgkin Building
Sarah L. Ferri: University of Iowa
Ted Abel: University of Iowa
Edward S. Brodkin: Perelman School of Medicine at the University of Pennsylvania
R. Jeroen Pasterkamp: University Medical Center Utrecht, Utrecht University
Brian P. Brooks: National Eye Institute, National Institutes of Health
Lia Panman: University of Cambridge, Hodgkin Building

Nature Communications, 2020, vol. 11, issue 1, 1-17

Abstract: 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.

Date: 2020
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DOI: 10.1038/s41467-020-16947-6

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