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Post-mitotic Prox1 expression controls the final specification of cortical VIP interneuron subtypes

View ORCID ProfileTevye Jason Stachniak, View ORCID ProfileRahel Kastli, View ORCID ProfileOlivia Hanley, View ORCID ProfileAli Özgür Argunsah, View ORCID ProfileTheofanis Karayannis
doi: https://doi.org/10.1101/2020.07.22.216135
Tevye Jason Stachniak
1Laboratory of Neural Circuit Assembly, Brain Research Institute, University of Zurich Winterthurerstrasse 190, CH-8057 Zurich, Switzerland
2Neuroscience Center Zurich, University of Zurich and ETH Zurich, Winterthurerstrasse 190, CH-8057 Zurich, Switzerland
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Rahel Kastli
1Laboratory of Neural Circuit Assembly, Brain Research Institute, University of Zurich Winterthurerstrasse 190, CH-8057 Zurich, Switzerland
2Neuroscience Center Zurich, University of Zurich and ETH Zurich, Winterthurerstrasse 190, CH-8057 Zurich, Switzerland
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Olivia Hanley
1Laboratory of Neural Circuit Assembly, Brain Research Institute, University of Zurich Winterthurerstrasse 190, CH-8057 Zurich, Switzerland
2Neuroscience Center Zurich, University of Zurich and ETH Zurich, Winterthurerstrasse 190, CH-8057 Zurich, Switzerland
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Ali Özgür Argunsah
1Laboratory of Neural Circuit Assembly, Brain Research Institute, University of Zurich Winterthurerstrasse 190, CH-8057 Zurich, Switzerland
2Neuroscience Center Zurich, University of Zurich and ETH Zurich, Winterthurerstrasse 190, CH-8057 Zurich, Switzerland
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Theofanis Karayannis
1Laboratory of Neural Circuit Assembly, Brain Research Institute, University of Zurich Winterthurerstrasse 190, CH-8057 Zurich, Switzerland
2Neuroscience Center Zurich, University of Zurich and ETH Zurich, Winterthurerstrasse 190, CH-8057 Zurich, Switzerland
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  • For correspondence: karayannis@hifo.uzh.ch
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Summary

Neuronal identity is controlled in multiple developmental steps by key transcription factors that determine the unique properties of a cell. During embryogenesis, the transcription factor Prox1 has been shown to regulate VIP interneuron migration, survival, and as a result, circuit integration. Here, we explore the role of Prox1 as a regulator of genetic programs that guide the final specification of VIP interneuron subtypes in early post-natal life. Using in-vitro electrophysiology we find that post-natal removal of Prox1 differentially affects the synaptic integration of VIP bipolar and multipolar subtypes.

RNA sequencing reveals that one of the downstream targets of Prox1 is the postsynaptic protein Elfn1, a constitutive regulator of presynaptic release probability. Genetic, pharmacological and electrophysiological experiments demonstrate that knocking out Prox1 reduces Elfn1 function in VIP multipolar but not in bipolar cells. Thus, in addition to the activity-dependent and contextual processes that finalize developmental trajectories, genetic programs engaged by Prox1 control the differentiation and connectivity of VIP interneuron subtypes.

Competing Interest Statement

The authors have declared no competing interest.

Copyright 
The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC 4.0 International license.
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Posted July 24, 2020.
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Post-mitotic Prox1 expression controls the final specification of cortical VIP interneuron subtypes
Tevye Jason Stachniak, Rahel Kastli, Olivia Hanley, Ali Özgür Argunsah, Theofanis Karayannis
bioRxiv 2020.07.22.216135; doi: https://doi.org/10.1101/2020.07.22.216135
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Post-mitotic Prox1 expression controls the final specification of cortical VIP interneuron subtypes
Tevye Jason Stachniak, Rahel Kastli, Olivia Hanley, Ali Özgür Argunsah, Theofanis Karayannis
bioRxiv 2020.07.22.216135; doi: https://doi.org/10.1101/2020.07.22.216135

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