---
OA_place: repository
OA_type: green
_id: '22961'
abstract:
- lang: eng
text: "## Rationale:\r\nDifferentiation trajectories to generate specialized cellular
features rely on sets of transcription factors (TFs) whose temporal dynamics and
coexistence underlie morphological and neurochemical divergence among neurons
and neuroendocrine cells. Even though transcriptional programs were extensively
studied in the developing nervous system, the coupling of TFs to effector gene
networks that time and shape the morphogenesis of these polarized cells is less
known.\r\n\r\n## Results:\r\nHere, we make the curious observation that evolutionarily
conserved Onecut3, a subordinate in the Onecut TF family known to control fate
selection in progenitors, is instead expressed in fate-restricted neuroblasts
in the vertebrate hypothalamus. In particular, a pool of Ascl1-containing progenitors
in the midgestational mouse hypothalamus gives rise to both GABA and glutamate
neurons destined to the periventricular and lateral hypothalamus, respectively,
which uniformly upregulate Onecut3 only when exiting the proliferative zone of
the 3rd ventricle. By combining single-cell RNA-seq, genetic Onecut3 reporters,
gain-of-function models in vitro, and loss-of-function analysis in early-developing
mice and C. elegans, we identify that Onecut3 instructs neuronal differentiation
and maturation, through a Navigator-2 pathway to modulate neuritogenesis and leading
process motility.\r\n\r\n\r\n## Conclusion:\r\nOnecut3 executes an unexpected
function by inducing cytoskeletal modifications of key importance for neuronal
maturation and network integration during the morphogenesis of many neuronal phenotypes
in the vertebrate hypothalamus."
article_processing_charge: No
author:
- first_name: Maja
full_name: Zupancic, Maja
last_name: Zupancic
- first_name: Erik
full_name: Keimpema, Erik
last_name: Keimpema
- first_name: Evgenii
full_name: Tretiakov, Evgenii
last_name: Tretiakov
- first_name: Pradeep
full_name: Bhandari, Pradeep
last_name: Bhandari
- first_name: Stephanie
full_name: Eder, Stephanie
last_name: Eder
- first_name: Itamar
full_name: Lev, Itamar
last_name: Lev
- first_name: Wolfgang
full_name: Härtig, Wolfgang
last_name: Härtig
- first_name: Manuel
full_name: Zimmer, Manuel
last_name: Zimmer
- first_name: Frederic
full_name: Clotman, Frederic
last_name: Clotman
- first_name: Tibor
full_name: Harkany, Tibor
last_name: Harkany
citation:
ama: Zupancic M, Keimpema E, Tretiakov E, et al. Glutamate and GABA neurons share
cascading Onecut3/NAV2-driven differentiation trajectories in the developing hypothalamus.
2023. doi:10.6084/m9.figshare.22680433
apa: Zupancic, M., Keimpema, E., Tretiakov, E., Bhandari, P., Eder, S., Lev, I.,
… Harkany, T. (2023). Glutamate and GABA neurons share cascading Onecut3/NAV2-driven
differentiation trajectories in the developing hypothalamus. Repository. https://doi.org/10.6084/m9.figshare.22680433
chicago: Zupancic, Maja, Erik Keimpema, Evgenii Tretiakov, Pradeep Bhandari, Stephanie
Eder, Itamar Lev, Wolfgang Härtig, Manuel Zimmer, Frederic Clotman, and Tibor
Harkany. “Glutamate and GABA Neurons Share Cascading Onecut3/NAV2-Driven Differentiation
Trajectories in the Developing Hypothalamus.” Repository, 2023. https://doi.org/10.6084/m9.figshare.22680433.
ieee: M. Zupancic et al., “Glutamate and GABA neurons share cascading Onecut3/NAV2-driven
differentiation trajectories in the developing hypothalamus.” Repository, 2023.
ista: Zupancic M, Keimpema E, Tretiakov E, Bhandari P, Eder S, Lev I, Härtig W,
Zimmer M, Clotman F, Harkany T. 2023. Glutamate and GABA neurons share cascading
Onecut3/NAV2-driven differentiation trajectories in the developing hypothalamus,
Repository, 10.6084/m9.figshare.22680433.
mla: Zupancic, Maja, et al. Glutamate and GABA Neurons Share Cascading Onecut3/NAV2-Driven
Differentiation Trajectories in the Developing Hypothalamus. Repository, 2023,
doi:10.6084/m9.figshare.22680433.
short: M. Zupancic, E. Keimpema, E. Tretiakov, P. Bhandari, S. Eder, I. Lev, W.
Härtig, M. Zimmer, F. Clotman, T. Harkany, (2023).
date_created: 2026-09-17T11:23:46Z
date_published: 2023-04-23T00:00:00Z
date_updated: 2026-10-01T12:17:26Z
day: '23'
ddc:
- '570'
department:
- _id: RySh
doi: 10.6084/m9.figshare.22680433
fulldoi: https://doi.org/10.6084/m9.figshare.22680433
main_file_link:
- open_access: '1'
url: https://doi.org/10.6084/m9.figshare.22680433
month: '04'
oa: 1
oa_version: None
publisher: Repository
related_material:
record:
- id: '18445'
relation: used_in_publication
status: public
status: public
title: Glutamate and GABA neurons share cascading Onecut3/NAV2-driven differentiation
trajectories in the developing hypothalamus
type: research_data_reference
user_id: 317138e5-6ab7-11ef-aa6d-ffef3953e345
year: '2023'
...