---
OA_place: publisher
_id: '9962'
abstract:
- lang: eng
  text: The brain is one of the largest and most complex organs and it is composed
    of billions of neurons that communicate together enabling e.g. consciousness.
    The cerebral cortex is the largest site of neural integration in the central nervous
    system. Concerted radial migration of newly born cortical projection neurons,
    from their birthplace to their final position, is a key step in the assembly of
    the cerebral cortex. The cellular and molecular mechanisms regulating radial neuronal
    migration in vivo are however still unclear. Recent evidence suggests that distinct
    signaling cues act cell-autonomously but differentially at certain steps during
    the overall migration process. Moreover, functional analysis of genetic mosaics
    (mutant neurons present in wild-type/heterozygote environment) using the MADM
    (Mosaic Analysis with Double Markers) analyses in comparison to global knockout
    also indicate a significant degree of non-cell-autonomous and/or community effects
    in the control of cortical neuron migration. The interactions of cell-intrinsic
    (cell-autonomous) and cell-extrinsic (non-cell-autonomous) components are largely
    unknown. In part of this thesis work we established a MADM-based experimental
    strategy for the quantitative analysis of cell-autonomous gene function versus
    non-cell-autonomous and/or community effects. The direct comparison of mutant
    neurons from the genetic mosaic (cell-autonomous) to mutant neurons in the conditional
    and/or global knockout (cell-autonomous + non-cell-autonomous) allows to quantitatively
    analyze non-cell-autonomous effects. Such analysis enable the high-resolution
    analysis of projection neuron migration dynamics in distinct environments with
    concomitant isolation of genomic and proteomic profiles. Using these experimental
    paradigms and in combination with computational modeling we show and characterize
    the nature of non-cell-autonomous effects to coordinate radial neuron migration.
    Furthermore, this thesis discusses recent developments in neurodevelopment with
    focus on neuronal polarization and non-cell-autonomous mechanisms in neuronal
    migration.
alternative_title:
- ISTA Thesis
article_processing_charge: No
author:
- first_name: Andi H
  full_name: Hansen, Andi H
  id: 38853E16-F248-11E8-B48F-1D18A9856A87
  last_name: Hansen
citation:
  ama: Hansen AH. Cell-autonomous gene function and non-cell-autonomous effects in
    radial projection neuron migration. 2021. doi:<a href="https://doi.org/10.15479/at:ista:9962">10.15479/at:ista:9962</a>
  apa: Hansen, A. H. (2021). <i>Cell-autonomous gene function and non-cell-autonomous
    effects in radial projection neuron migration</i>. Institute of Science and Technology
    Austria. <a href="https://doi.org/10.15479/at:ista:9962">https://doi.org/10.15479/at:ista:9962</a>
  chicago: Hansen, Andi H. “Cell-Autonomous Gene Function and Non-Cell-Autonomous
    Effects in Radial Projection Neuron Migration.” Institute of Science and Technology
    Austria, 2021. <a href="https://doi.org/10.15479/at:ista:9962">https://doi.org/10.15479/at:ista:9962</a>.
  ieee: A. H. Hansen, “Cell-autonomous gene function and non-cell-autonomous effects
    in radial projection neuron migration,” Institute of Science and Technology Austria,
    2021.
  ista: Hansen AH. 2021. Cell-autonomous gene function and non-cell-autonomous effects
    in radial projection neuron migration. Institute of Science and Technology Austria.
  mla: Hansen, Andi H. <i>Cell-Autonomous Gene Function and Non-Cell-Autonomous Effects
    in Radial Projection Neuron Migration</i>. Institute of Science and Technology
    Austria, 2021, doi:<a href="https://doi.org/10.15479/at:ista:9962">10.15479/at:ista:9962</a>.
  short: A.H. Hansen, Cell-Autonomous Gene Function and Non-Cell-Autonomous Effects
    in Radial Projection Neuron Migration, Institute of Science and Technology Austria,
    2021.
corr_author: '1'
date_created: 2021-08-29T12:36:50Z
date_published: 2021-09-02T00:00:00Z
date_updated: 2026-04-08T07:19:09Z
day: '02'
ddc:
- '570'
degree_awarded: PhD
department:
- _id: GradSch
- _id: SiHi
doi: 10.15479/at:ista:9962
file:
- access_level: closed
  checksum: 66b56f5b988b233dc66a4f4b4fb2cdfe
  content_type: application/vnd.openxmlformats-officedocument.wordprocessingml.document
  creator: ahansen
  date_created: 2021-08-30T09:17:39Z
  date_updated: 2022-09-03T22:30:04Z
  embargo_to: open_access
  file_id: '9971'
  file_name: Thesis_Hansen.docx
  file_size: 10629190
  relation: source_file
- access_level: open_access
  checksum: 204fa40321a1c6289b68c473634c4bf3
  content_type: application/pdf
  creator: ahansen
  date_created: 2021-08-30T09:29:44Z
  date_updated: 2022-09-03T22:30:04Z
  embargo: 2022-09-02
  file_id: '9972'
  file_name: Thesis_Hansen_PDFA-1a.pdf
  file_size: 13457469
  relation: main_file
file_date_updated: 2022-09-03T22:30:04Z
has_accepted_license: '1'
keyword:
- Neuronal migration
- Non-cell-autonomous
- Cell-autonomous
- Neurodevelopmental disease
language:
- iso: eng
license: https://creativecommons.org/licenses/by/4.0/
month: '09'
oa: 1
oa_version: Published Version
page: '182'
project:
- _id: 2625A13E-B435-11E9-9278-68D0E5697425
  grant_number: '24812'
  name: Molecular mechanisms of radial neuronal migration
publication_identifier:
  issn:
  - 2663-337X
publication_status: published
publisher: Institute of Science and Technology Austria
related_material:
  record:
  - id: '8569'
    relation: part_of_dissertation
    status: public
  - id: '960'
    relation: part_of_dissertation
    status: public
status: public
supervisor:
- first_name: Simon
  full_name: Hippenmeyer, Simon
  id: 37B36620-F248-11E8-B48F-1D18A9856A87
  last_name: Hippenmeyer
  orcid: 0000-0003-2279-1061
title: Cell-autonomous gene function and non-cell-autonomous effects in radial projection
  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: dissertation
user_id: ba8df636-2132-11f1-aed0-ed93e2281fdd
year: '2021'
...
---
_id: '3396'
abstract:
- lang: eng
  text: Facial branchiomotor neurons (FBMNs) in zebrafish and mouse embryonic hindbrain
    undergo a characteristic tangential migration from rhombomere (r) 4, where they
    are born, to r6/7. Cohesion among neuroepithelial cells (NCs) has been suggested
    to function in FBMN migration by inhibiting FBMNs positioned in the basal neuroepithelium
    such that they move apically between NCs towards the midline of the neuroepithelium
    instead of tangentially along the basal side of the neuroepithelium towards r6/7.
    However, direct experimental evaluation of this hypothesis is still lacking. Here,
    we have used a combination of biophysical cell adhesion measurements and high-resolution
    time-lapse microscopy to determine the role of NC cohesion in FBMN migration.
    We show that reducing NC cohesion by interfering with Cadherin 2 (Cdh2) activity
    results in FBMNs positioned at the basal side of the neuroepithelium moving apically
    towards the neural tube midline instead of tangentially towards r6/7. In embryos
    with strongly reduced NC cohesion, ectopic apical FBMN movement frequently results
    in fusion of the bilateral FBMN clusters over the apical midline of the neural
    tube. By contrast, reducing cohesion among FBMNs by interfering with Contactin
    2 (Cntn2) expression in these cells has little effect on apical FBMN movement,
    but reduces the fusion of the bilateral FBMN clusters in embryos with strongly
    diminished NC cohesion. These data provide direct experimental evidence that NC
    cohesion functions in tangential FBMN migration by restricting their apical movement.
acknowledged_ssus:
- _id: Bio
- _id: PreCl
acknowledgement: We thank C. Moens and J. Geiger for critical reading of earlier versions
  of this manuscript and members of the Heisenberg laboratory for discussions. We
  are grateful to the microscopy facility of the MPI-CBG and IST Austria for continuous
  support; I. Nüsslein, J. Compagnon and Alex Eichner for help with cell sorting;
  and the fish facility of the MPI-CBG and IST Austria for excellent fish care.
article_processing_charge: No
article_type: original
author:
- first_name: Petra
  full_name: Stockinger, Petra
  id: 261CB030-E90D-11E9-B182-F697D44B663C
  last_name: Stockinger
- first_name: Carl-Philipp J
  full_name: Heisenberg, Carl-Philipp J
  id: 39427864-F248-11E8-B48F-1D18A9856A87
  last_name: Heisenberg
  orcid: 0000-0002-0912-4566
- first_name: Jean-Léon
  full_name: Maître, Jean-Léon
  id: 48F1E0D8-F248-11E8-B48F-1D18A9856A87
  last_name: Maître
  orcid: 0000-0002-3688-1474
citation:
  ama: Stockinger P, Heisenberg C-PJ, Maître J-L. Defective neuroepithelial cell cohesion
    affects tangential branchiomotor neuron migration in the zebrafish neural tube.
    <i>Development</i>. 2011;138(21):4673-4683. doi:<a href="https://doi.org/10.1242/dev.071233">10.1242/dev.071233</a>
  apa: Stockinger, P., Heisenberg, C.-P. J., &#38; Maître, J.-L. (2011). Defective
    neuroepithelial cell cohesion affects tangential branchiomotor neuron migration
    in the zebrafish neural tube. <i>Development</i>. Company of Biologists. <a href="https://doi.org/10.1242/dev.071233">https://doi.org/10.1242/dev.071233</a>
  chicago: Stockinger, Petra, Carl-Philipp J Heisenberg, and Jean-Léon Maître. “Defective
    Neuroepithelial Cell Cohesion Affects Tangential Branchiomotor Neuron Migration
    in the Zebrafish Neural Tube.” <i>Development</i>. Company of Biologists, 2011.
    <a href="https://doi.org/10.1242/dev.071233">https://doi.org/10.1242/dev.071233</a>.
  ieee: P. Stockinger, C.-P. J. Heisenberg, and J.-L. Maître, “Defective neuroepithelial
    cell cohesion affects tangential branchiomotor neuron migration in the zebrafish
    neural tube,” <i>Development</i>, vol. 138, no. 21. Company of Biologists, pp.
    4673–4683, 2011.
  ista: Stockinger P, Heisenberg C-PJ, Maître J-L. 2011. Defective neuroepithelial
    cell cohesion affects tangential branchiomotor neuron migration in the zebrafish
    neural tube. Development. 138(21), 4673–4683.
  mla: Stockinger, Petra, et al. “Defective Neuroepithelial Cell Cohesion Affects
    Tangential Branchiomotor Neuron Migration in the Zebrafish Neural Tube.” <i>Development</i>,
    vol. 138, no. 21, Company of Biologists, 2011, pp. 4673–83, doi:<a href="https://doi.org/10.1242/dev.071233">10.1242/dev.071233</a>.
  short: P. Stockinger, C.-P.J. Heisenberg, J.-L. Maître, Development 138 (2011) 4673–4683.
corr_author: '1'
date_created: 2018-12-11T12:03:06Z
date_published: 2011-11-01T00:00:00Z
date_updated: 2026-07-28T08:23:30Z
day: '01'
ddc:
- '570'
department:
- _id: CaHe
doi: 10.1242/dev.071233
external_id:
  isi:
  - '000296060100011'
file:
- access_level: open_access
  checksum: ca12b79e01ef36c1ef1aea31cf7e7139
  content_type: application/pdf
  creator: dernst
  date_created: 2019-10-07T14:19:42Z
  date_updated: 2020-07-14T12:46:12Z
  file_id: '6930'
  file_name: 2011_Development_Stockinger.pdf
  file_size: 4672439
  relation: main_file
file_date_updated: 2020-07-14T12:46:12Z
has_accepted_license: '1'
intvolume: '       138'
isi: 1
issue: '21'
keyword:
- Epithelial cohesion
- Hindbrain
- Neuronal migration
- Zebrafish
language:
- iso: eng
month: '11'
oa: 1
oa_version: Published Version
page: 4673 - 4683
publication: Development
publication_status: published
publisher: Company of Biologists
publist_id: '3210'
quality_controlled: '1'
scopus_import: '1'
status: public
title: Defective neuroepithelial cell cohesion affects tangential branchiomotor neuron
  migration in the zebrafish neural tube
type: journal_article
user_id: 2DF688A6-F248-11E8-B48F-1D18A9856A87
volume: 138
year: '2011'
...