Postmitotic Prox1 Expression Controls the Final Specification of Cortical VIP Interneuron Subtypes
Throughout development, neuronal identity is controlled by key transcription factors that determine the unique properties of a cell. During embryogenesis, the transcription factor Prox1 regulates VIP-positive cortical interneuron migration, survival, and connectivity. Here, we explore the role of Pr...
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| Veröffentlicht in: | The Journal of neuroscience 2021-09, Vol.41 (39), p.8150-8162 |
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| container_title | The Journal of neuroscience |
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| creator | Stachniak, Tevye Jason Kastli, Rahel Hanley, Olivia Argunsah, Ali Özgür van der Valk, Elianne Grietje Theodora Kanatouris, George Karayannis, Theofanis |
| description | Throughout development, neuronal identity is controlled by key transcription factors that determine the unique properties of a cell. During embryogenesis, the transcription factor Prox1 regulates VIP-positive cortical interneuron migration, survival, and connectivity. Here, we explore the role of Prox1 as a regulator of genetic programs that guide the final specification of VIP interneuron subtypes in early postnatal life. Synaptic in vitro electrophysiology in male and female mice shows that postnatal Prox1 removal differentially affects the dynamics of excitatory inputs onto 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. Further genetic, pharmacological, and electrophysiological experiments demonstrate that removing Prox1 reduces Elfn1 function in VIP multipolar but not in bipolar cells. Finally, overexpression experiments and analysis of native Elfn1 mRNA expression reveal that Elfn1 levels are differentially controlled at the post-transcriptional stage. Thus, in addition to activity-dependent processes that contribute to the developmental trajectory of VIP cells, genetic programs engaged by Prox1 control the final differentiation of multipolar and bipolar subtypes. |
| doi_str_mv | 10.1523/JNEUROSCI.1021-21.2021 |
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During embryogenesis, the transcription factor Prox1 regulates VIP-positive cortical interneuron migration, survival, and connectivity. Here, we explore the role of Prox1 as a regulator of genetic programs that guide the final specification of VIP interneuron subtypes in early postnatal life. Synaptic in vitro electrophysiology in male and female mice shows that postnatal Prox1 removal differentially affects the dynamics of excitatory inputs onto 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. Further genetic, pharmacological, and electrophysiological experiments demonstrate that removing Prox1 reduces Elfn1 function in VIP multipolar but not in bipolar cells. Finally, overexpression experiments and analysis of native Elfn1 mRNA expression reveal that Elfn1 levels are differentially controlled at the post-transcriptional stage. Thus, in addition to activity-dependent processes that contribute to the developmental trajectory of VIP cells, genetic programs engaged by Prox1 control the final differentiation of multipolar and bipolar subtypes.</description><identifier>ISSN: 0270-6474</identifier><identifier>EISSN: 1529-2401</identifier><identifier>DOI: 10.1523/JNEUROSCI.1021-21.2021</identifier><identifier>PMID: 34380763</identifier><language>eng</language><publisher>Baltimore: Society for Neuroscience</publisher><subject>Bipolar cells ; Electrophysiology ; Embryogenesis ; Embryonic growth stage ; Gene expression ; Gene sequencing ; Genetic programs ; Neural networks ; Post-transcription ; Specifications ; Transcription factors</subject><ispartof>The Journal of neuroscience, 2021-09, Vol.41 (39), p.8150-8162</ispartof><rights>Copyright Society for Neuroscience Sep 29, 2021</rights><rights>Copyright © 2021 Stachniak, Kastli et al. 2021</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c419t-cfc7e4185757f734fe8fb7a64e1195cb0ebe1e95a7fef20d2a2a6608bd7d15993</citedby><orcidid>0000-0003-3801-1621 ; 0000-0002-3082-3775 ; 0000-0003-2498-5783</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC8482865/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC8482865/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,723,776,780,881,27903,27904,53770,53772</link.rule.ids></links><search><creatorcontrib>Stachniak, Tevye Jason</creatorcontrib><creatorcontrib>Kastli, Rahel</creatorcontrib><creatorcontrib>Hanley, Olivia</creatorcontrib><creatorcontrib>Argunsah, Ali Özgür</creatorcontrib><creatorcontrib>van der Valk, Elianne Grietje Theodora</creatorcontrib><creatorcontrib>Kanatouris, George</creatorcontrib><creatorcontrib>Karayannis, Theofanis</creatorcontrib><title>Postmitotic Prox1 Expression Controls the Final Specification of Cortical VIP Interneuron Subtypes</title><title>The Journal of neuroscience</title><description>Throughout development, neuronal identity is controlled by key transcription factors that determine the unique properties of a cell. 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| subjects | Bipolar cells Electrophysiology Embryogenesis Embryonic growth stage Gene expression Gene sequencing Genetic programs Neural networks Post-transcription Specifications Transcription factors |
| title | Postmitotic Prox1 Expression Controls the Final Specification of Cortical VIP Interneuron Subtypes |
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