---
_id: '10791'
abstract:
- lang: eng
  text: The mammalian neocortex is composed of diverse neuronal and glial cell classes
    that broadly arrange in six distinct laminae. Cortical layers emerge during development
    and defects in the developmental programs that orchestrate cortical lamination
    are associated with neurodevelopmental diseases. The developmental principle of
    cortical layer formation depends on concerted radial projection neuron migration,
    from their birthplace to their final target position. Radial migration occurs
    in defined sequential steps, regulated by a large array of signaling pathways.
    However, based on genetic loss-of-function experiments, most studies have thus
    far focused on the role of cell-autonomous gene function. Yet, cortical neuron
    migration in situ is a complex process and migrating neurons traverse along diverse
    cellular compartments and environments. The role of tissue-wide properties and
    genetic state in radial neuron migration is however not clear. Here we utilized
    mosaic analysis with double markers (MADM) technology to either sparsely or globally
    delete gene function, followed by quantitative single-cell phenotyping. The MADM-based
    gene ablation paradigms in combination with computational modeling demonstrated
    that global tissue-wide effects predominate cell-autonomous gene function albeit
    in a gene-specific manner. Our results thus suggest that the genetic landscape
    in a tissue critically affects the overall migration phenotype of individual cortical
    projection neurons. In a broader context, our findings imply that global tissue-wide
    effects represent an essential component of the underlying etiology associated
    with focal malformations of cortical development in particular, and neurological
    diseases in general.
acknowledged_ssus:
- _id: LifeSc
- _id: PreCl
- _id: Bio
acknowledgement: "A.H.H. was a recipient of a DOC Fellowship (24812) of the Austrian
  Academy of Sciences. This work also received support from IST Austria institutional
  funds; the People Programme (Marie Curie Actions) of the European Union’s Seventh
  Framework Programme (FP7/2007–2013) under REA grant agreement No 618444 to S.H.\r\nAPC
  funding was obtained by IST Austria institutional funds.\r\nWe thank A. Sommer and
  C. Czepe (VBCF GmbH, NGS Unit), L. Andersen, J. Sonntag and J. Renno for technical
  support and/or initial experiments; M. Sixt, J. Nimpf and all members of the Hippenmeyer
  lab for discussion. This research was supported by the Scientific Service Units
  of IST Austria through resources provided by the Imaging and Optics Facility, Lab
  Support Facility and Preclinical Facility."
article_number: kvac009
article_processing_charge: No
article_type: original
author:
- first_name: Andi H
  full_name: Hansen, Andi H
  id: 38853E16-F248-11E8-B48F-1D18A9856A87
  last_name: Hansen
- first_name: Florian
  full_name: Pauler, Florian
  id: 48EA0138-F248-11E8-B48F-1D18A9856A87
  last_name: Pauler
  orcid: 0000-0002-7462-0048
- first_name: Michael
  full_name: Riedl, Michael
  id: 3BE60946-F248-11E8-B48F-1D18A9856A87
  last_name: Riedl
  orcid: 0000-0003-4844-6311
- first_name: Carmen
  full_name: Streicher, Carmen
  id: 36BCB99C-F248-11E8-B48F-1D18A9856A87
  last_name: Streicher
- first_name: Anna-Magdalena
  full_name: Heger, Anna-Magdalena
  id: 4B76FFD2-F248-11E8-B48F-1D18A9856A87
  last_name: Heger
- first_name: Susanne
  full_name: Laukoter, Susanne
  id: 2D6B7A9A-F248-11E8-B48F-1D18A9856A87
  last_name: Laukoter
  orcid: 0000-0002-7903-3010
- first_name: Christoph M
  full_name: Sommer, Christoph M
  id: 4DF26D8C-F248-11E8-B48F-1D18A9856A87
  last_name: Sommer
  orcid: 0000-0003-1216-9105
- first_name: Armel
  full_name: Nicolas, Armel
  id: 2A103192-F248-11E8-B48F-1D18A9856A87
  last_name: Nicolas
- first_name: Björn
  full_name: Hof, Björn
  id: 3A374330-F248-11E8-B48F-1D18A9856A87
  last_name: Hof
  orcid: 0000-0003-2057-2754
- first_name: Li Huei
  full_name: Tsai, Li Huei
  last_name: Tsai
- first_name: Thomas
  full_name: Rülicke, Thomas
  last_name: Rülicke
- first_name: Simon
  full_name: Hippenmeyer, Simon
  id: 37B36620-F248-11E8-B48F-1D18A9856A87
  last_name: Hippenmeyer
  orcid: 0000-0003-2279-1061
citation:
  ama: Hansen AH, Pauler F, Riedl M, et al. Tissue-wide effects override cell-intrinsic
    gene function in radial neuron migration. <i>Oxford Open Neuroscience</i>. 2022;1(1).
    doi:<a href="https://doi.org/10.1093/oons/kvac009">10.1093/oons/kvac009</a>
  apa: Hansen, A. H., Pauler, F., Riedl, M., Streicher, C., Heger, A.-M., Laukoter,
    S., … Hippenmeyer, S. (2022). Tissue-wide effects override cell-intrinsic gene
    function in radial neuron migration. <i>Oxford Open Neuroscience</i>. Oxford Academic.
    <a href="https://doi.org/10.1093/oons/kvac009">https://doi.org/10.1093/oons/kvac009</a>
  chicago: Hansen, Andi H, Florian Pauler, Michael Riedl, Carmen Streicher, Anna-Magdalena
    Heger, Susanne Laukoter, Christoph M Sommer, et al. “Tissue-Wide Effects Override
    Cell-Intrinsic Gene Function in Radial Neuron Migration.” <i>Oxford Open Neuroscience</i>.
    Oxford Academic, 2022. <a href="https://doi.org/10.1093/oons/kvac009">https://doi.org/10.1093/oons/kvac009</a>.
  ieee: A. H. Hansen <i>et al.</i>, “Tissue-wide effects override cell-intrinsic gene
    function in radial neuron migration,” <i>Oxford Open Neuroscience</i>, vol. 1,
    no. 1. Oxford Academic, 2022.
  ista: Hansen AH, Pauler F, Riedl M, Streicher C, Heger A-M, Laukoter S, Sommer CM,
    Nicolas A, Hof B, Tsai LH, Rülicke T, Hippenmeyer S. 2022. Tissue-wide effects
    override cell-intrinsic gene function in radial neuron migration. Oxford Open
    Neuroscience. 1(1), kvac009.
  mla: Hansen, Andi H., et al. “Tissue-Wide Effects Override Cell-Intrinsic Gene Function
    in Radial Neuron Migration.” <i>Oxford Open Neuroscience</i>, vol. 1, no. 1, kvac009,
    Oxford Academic, 2022, doi:<a href="https://doi.org/10.1093/oons/kvac009">10.1093/oons/kvac009</a>.
  short: A.H. Hansen, F. Pauler, M. Riedl, C. Streicher, A.-M. Heger, S. Laukoter,
    C.M. Sommer, A. Nicolas, B. Hof, L.H. Tsai, T. Rülicke, S. Hippenmeyer, Oxford
    Open Neuroscience 1 (2022).
date_created: 2022-02-25T07:52:11Z
date_published: 2022-07-07T00:00:00Z
date_updated: 2023-11-30T10:55:12Z
day: '07'
ddc:
- '570'
department:
- _id: SiHi
- _id: BjHo
- _id: LifeSc
- _id: EM-Fac
doi: 10.1093/oons/kvac009
ec_funded: 1
file:
- access_level: open_access
  checksum: 822e76e056c07099d1fb27d1ece5941b
  content_type: application/pdf
  creator: dernst
  date_created: 2023-08-16T08:00:30Z
  date_updated: 2023-08-16T08:00:30Z
  file_id: '14061'
  file_name: 2023_OxfordOpenNeuroscience_Hansen.pdf
  file_size: 4846551
  relation: main_file
  success: 1
file_date_updated: 2023-08-16T08:00:30Z
has_accepted_license: '1'
intvolume: '         1'
issue: '1'
language:
- iso: eng
month: '07'
oa: 1
oa_version: Published Version
project:
- _id: 25D61E48-B435-11E9-9278-68D0E5697425
  call_identifier: FP7
  grant_number: '618444'
  name: Molecular Mechanisms of Cerebral Cortex Development
- _id: 2625A13E-B435-11E9-9278-68D0E5697425
  grant_number: '24812'
  name: Molecular Mechanisms of Radial Neuronal Migration
publication: Oxford Open Neuroscience
publication_identifier:
  eissn:
  - 2753-149X
publication_status: published
publisher: Oxford Academic
quality_controlled: '1'
related_material:
  record:
  - id: '12726'
    relation: dissertation_contains
    status: public
  - id: '14530'
    relation: dissertation_contains
    status: public
status: public
title: Tissue-wide effects override cell-intrinsic gene function in radial neuron
  migration
tmp:
  image: /images/cc_by.png
  legal_code_url: https://creativecommons.org/licenses/by/4.0/legalcode
  name: Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)
  short: CC BY (4.0)
type: journal_article
user_id: 2DF688A6-F248-11E8-B48F-1D18A9856A87
volume: 1
year: '2022'
...