Postmitotic Hoxa5 Expression Specifies Pontine Neuron Positional Identity and Input Connectivity of Cortical Afferent Subsets

Maheshwari, Upasana and Kraus, Dominik and Vilain, Nathalie and Holwerda, Sjoerd J. B. and Cankovic, Vanja and Maiorano, Nicola A. and Kohler, Hubertus and Satoh, Daisuke and Sigrist, Markus and Arber, Silvia and Kratochwil, Claudius F. and Di Meglio, Thomas and Ducret, Sebastien and Rijli, Filippo M.. (2020) Postmitotic Hoxa5 Expression Specifies Pontine Neuron Positional Identity and Input Connectivity of Cortical Afferent Subsets. Cell reports, 31 (11). p. 107767.

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Official URL: https://edoc.unibas.ch/78942/

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The mammalian precerebellar pontine nucleus (PN) has a main role in relaying cortical information to the cerebellum. The molecular determinants establishing ordered connectivity patterns between cortical afferents and precerebellar neurons are largely unknown. We show that expression of Hox5 transcription factors is induced in specific subsets of postmitotic PN neurons at migration onset. Hox5 induction is achieved by response to retinoic acid signaling, resulting in Jmjd3-dependent derepression of Polycomb chromatin and 3D conformational changes. Hoxa5 drives neurons to settle posteriorly in the PN, where they are monosynaptically targeted by cortical neuron subsets mainly carrying limb somatosensation. Furthermore, Hoxa5 postmigratory ectopic expression in PN neurons is sufficient to attract cortical somatosensory inputs regardless of position and avoid visual afferents. Transcriptome analysis further suggests that Hoxa5 is involved in circuit formation. Thus, Hoxa5 coordinates postmitotic specification, migration, settling position, and sub-circuit assembly of PN neuron subsets in the cortico-cerebellar pathway.
Faculties and Departments:05 Faculty of Science > Departement Biozentrum > Neurobiology > Cell Biology (Arber)
09 Associated Institutions > Friedrich Miescher Institut FMI
UniBasel Contributors:Arber, Silvia and Sigrist, Markus
Item Type:Article, refereed
Article Subtype:Research Article
Note:Publication type according to Uni Basel Research Database: Journal article
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Last Modified:26 Jan 2022 15:48
Deposited On:26 Jan 2022 15:48

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