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

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Datum

2020

Autor:innen

Maheshwari, Upasana
Kraus, Dominik
Vilain, Nathalie
Maiorano, Nicola A.
Kohler, Hubertus
Satoh, Daisuke
Sigrist, Markus
Holwerda, Sjoerd J. B.
Cankovic, Vanja
et al.

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Cell reports. Cell Press. 2020, 31(11), 107767. ISSN 2211-1247. eISSN 2211-1247. Available under: doi: 10.1016/j.celrep.2020.107767

Zusammenfassung

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.

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Fachgebiet (DDC)
570 Biowissenschaften, Biologie

Schlagwörter

Hox transcription factor, corticopontine circuit development, precerebellar neurons, retinoic acid, neuronal positional identity, somatosensory topographic connectivity map, epigenetic chromatin regulation, transsynaptic neuronal tracing, Ezh2, Kdm6b

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ISO 690MAHESHWARI, Upasana, Dominik KRAUS, Nathalie VILAIN, Nicola A. MAIORANO, Hubertus KOHLER, Daisuke SATOH, Markus SIGRIST, Claudius F. KRATOCHWIL, Sjoerd J. B. HOLWERDA, Vanja CANKOVIC, 2020. Postmitotic Hoxa5 Expression Specifies Pontine Neuron Positional Identity and Input Connectivity of Cortical Afferent Subsets. In: Cell reports. Cell Press. 2020, 31(11), 107767. ISSN 2211-1247. eISSN 2211-1247. Available under: doi: 10.1016/j.celrep.2020.107767
BibTex
@article{Maheshwari2020-06-16Postm-50655,
  year={2020},
  doi={10.1016/j.celrep.2020.107767},
  title={Postmitotic Hoxa5 Expression Specifies Pontine Neuron Positional Identity and Input Connectivity of Cortical Afferent Subsets},
  number={11},
  volume={31},
  issn={2211-1247},
  journal={Cell reports},
  author={Maheshwari, Upasana and Kraus, Dominik and Vilain, Nathalie and Maiorano, Nicola A. and Kohler, Hubertus and Satoh, Daisuke and Sigrist, Markus and Kratochwil, Claudius F. and Holwerda, Sjoerd J. B. and Cankovic, Vanja},
  note={Article Number: 107767}
}
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