---
_id: '14323'
abstract:
- lang: eng
  text: Morphogens are signaling molecules that are known for their prominent role
    in pattern formation within developing tissues. In addition to patterning, morphogens
    also control tissue growth. However, the underlying mechanisms are poorly understood.
    We studied the role of morphogens in regulating tissue growth in the developing
    vertebrate neural tube. In this system, opposing morphogen gradients of Shh and
    BMP establish the dorsoventral pattern of neural progenitor domains. Perturbations
    in these morphogen pathways result in alterations in tissue growth and cell cycle
    progression, however, it has been unclear what cellular process is affected. To
    address this, we analysed the rates of cell proliferation and cell death in mouse
    mutants in which signaling is perturbed, as well as in chick neural plate explants
    exposed to defined concentrations of signaling activators or inhibitors. Our results
    indicated that the rate of cell proliferation was not altered in these assays.
    By contrast, both the Shh and BMP signaling pathways had profound effects on neural
    progenitor survival. Our results indicate that these pathways synergise to promote
    cell survival within neural progenitors. Consistent with this, we found that progenitors
    within the intermediate region of the neural tube, where the combined levels of
    Shh and BMP are the lowest, are most prone to cell death when signaling activity
    is inhibited. In addition, we found that downregulation of Shh results in increased
    apoptosis within the roof plate, which is the dorsal source of BMP ligand production.
    This revealed a cross-interaction between the Shh and BMP morphogen signaling
    pathways that may be relevant for understanding how gradients scale in neural
    tubes with different overall sizes. We further studied the mechanism acting downstream
    of Shh in cell survival regulation using genetic and genomic approaches. We propose
    that Shh transcriptionally regulates a non-canonical apoptotic pathway. Altogether,
    our study points to a novel role of opposing morphogen gradients in tissue size
    regulation and provides new insights into complex interactions between Shh and
    BMP signaling gradients in the neural tube.
acknowledged_ssus:
- _id: Bio
- _id: PreCl
alternative_title:
- ISTA Thesis
article_processing_charge: No
author:
- first_name: Katarzyna
  full_name: Kuzmicz-Kowalska, Katarzyna
  id: 4CED352A-F248-11E8-B48F-1D18A9856A87
  last_name: Kuzmicz-Kowalska
citation:
  ama: Kuzmicz-Kowalska K. Regulation of neural progenitor survival by Shh and BMP
    in the developing spinal cord. 2023. doi:<a href="https://doi.org/10.15479/at:ista:14323">10.15479/at:ista:14323</a>
  apa: Kuzmicz-Kowalska, K. (2023). <i>Regulation of neural progenitor survival by
    Shh and BMP in the developing spinal cord</i>. Institute of Science and Technology
    Austria. <a href="https://doi.org/10.15479/at:ista:14323">https://doi.org/10.15479/at:ista:14323</a>
  chicago: Kuzmicz-Kowalska, Katarzyna. “Regulation of Neural Progenitor Survival
    by Shh and BMP in the Developing Spinal Cord.” Institute of Science and Technology
    Austria, 2023. <a href="https://doi.org/10.15479/at:ista:14323">https://doi.org/10.15479/at:ista:14323</a>.
  ieee: K. Kuzmicz-Kowalska, “Regulation of neural progenitor survival by Shh and
    BMP in the developing spinal cord,” Institute of Science and Technology Austria,
    2023.
  ista: Kuzmicz-Kowalska K. 2023. Regulation of neural progenitor survival by Shh
    and BMP in the developing spinal cord. Institute of Science and Technology Austria.
  mla: Kuzmicz-Kowalska, Katarzyna. <i>Regulation of Neural Progenitor Survival by
    Shh and BMP in the Developing Spinal Cord</i>. Institute of Science and Technology
    Austria, 2023, doi:<a href="https://doi.org/10.15479/at:ista:14323">10.15479/at:ista:14323</a>.
  short: K. Kuzmicz-Kowalska, Regulation of Neural Progenitor Survival by Shh and
    BMP in the Developing Spinal Cord, Institute of Science and Technology Austria,
    2023.
date_created: 2023-09-13T10:07:18Z
date_published: 2023-09-13T00:00:00Z
date_updated: 2024-03-07T15:02:59Z
day: '13'
ddc:
- '570'
degree_awarded: PhD
department:
- _id: GradSch
- _id: AnKi
doi: 10.15479/at:ista:14323
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language:
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month: '09'
oa_version: Published Version
page: '151'
project:
- _id: 267AF0E4-B435-11E9-9278-68D0E5697425
  name: The role of morphogens in the regulation of neural tube growth
publication_identifier:
  issn:
  - 2663 - 337X
publication_status: published
publisher: Institute of Science and Technology Austria
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status: public
supervisor:
- first_name: Anna
  full_name: Kicheva, Anna
  id: 3959A2A0-F248-11E8-B48F-1D18A9856A87
  last_name: Kicheva
  orcid: 0000-0003-4509-4998
title: Regulation of neural progenitor survival by Shh and BMP in the developing spinal
  cord
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type: dissertation
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year: '2023'
...
---
_id: '13081'
abstract:
- lang: eng
  text: During development, tissues undergo changes in size and shape to form functional
    organs. Distinct cellular processes such as cell division and cell rearrangements
    underlie tissue morphogenesis. Yet how the distinct processes are controlled and
    coordinated, and how they contribute to morphogenesis is poorly understood. In
    our study, we addressed these questions using the developing mouse neural tube.
    This epithelial organ transforms from a flat epithelial sheet to an epithelial
    tube while increasing in size and undergoing morpho-gen-mediated patterning. The
    extent and mechanism of neural progenitor rearrangement within the developing
    mouse neuroepithelium is unknown. To investigate this, we per-formed high resolution
    lineage tracing analysis to quantify the extent of epithelial rear-rangement at
    different stages of neural tube development. We quantitatively described the relationship
    between apical cell size with cell cycle dependent interkinetic nuclear migra-tions
    (IKNM) and performed high cellular resolution live imaging of the neuroepithelium
    to study the dynamics of junctional remodeling.  Furthermore, developed a vertex
    model of the neuroepithelium to investigate the quantitative contribution of cell
    proliferation, cell differentiation and mechanical properties to the epithelial
    rearrangement dynamics and validated the model predictions through functional
    experiments. Our analysis revealed that at early developmental stages, the apical
    cell area kinetics driven by IKNM induce high lev-els of cell rearrangements in
    a regime of high junctional tension and contractility. After E9.5, there is a
    sharp decline in the extent of cell rearrangements, suggesting that the epi-thelium
    transitions from a fluid-like to a solid-like state. We found that this transition
    is regulated by the growth rate of the tissue, rather than by changes in cell-cell
    adhesion and contractile forces. Overall, our study provides a quantitative description
    of the relationship between tissue growth, cell cycle dynamics, epithelia rearrangements
    and the emergent tissue material properties, and novel insights on how epithelial
    cell dynamics influences tissue morphogenesis.
acknowledged_ssus:
- _id: Bio
- _id: LifeSc
alternative_title:
- ISTA Thesis
article_processing_charge: No
author:
- first_name: Laura
  full_name: Bocanegra, Laura
  id: 4896F754-F248-11E8-B48F-1D18A9856A87
  last_name: Bocanegra
citation:
  ama: Bocanegra L. Epithelial dynamics during mouse neural tube development. 2023.
    doi:<a href="https://doi.org/10.15479/at:ista:13081">10.15479/at:ista:13081</a>
  apa: Bocanegra, L. (2023). <i>Epithelial dynamics during mouse neural tube development</i>.
    Institute of Science and Technology Austria. <a href="https://doi.org/10.15479/at:ista:13081">https://doi.org/10.15479/at:ista:13081</a>
  chicago: Bocanegra, Laura. “Epithelial Dynamics during Mouse Neural Tube Development.”
    Institute of Science and Technology Austria, 2023. <a href="https://doi.org/10.15479/at:ista:13081">https://doi.org/10.15479/at:ista:13081</a>.
  ieee: L. Bocanegra, “Epithelial dynamics during mouse neural tube development,”
    Institute of Science and Technology Austria, 2023.
  ista: Bocanegra L. 2023. Epithelial dynamics during mouse neural tube development.
    Institute of Science and Technology Austria.
  mla: Bocanegra, Laura. <i>Epithelial Dynamics during Mouse Neural Tube Development</i>.
    Institute of Science and Technology Austria, 2023, doi:<a href="https://doi.org/10.15479/at:ista:13081">10.15479/at:ista:13081</a>.
  short: L. Bocanegra, Epithelial Dynamics during Mouse Neural Tube Development, Institute
    of Science and Technology Austria, 2023.
date_created: 2023-05-23T19:10:42Z
date_published: 2023-05-23T00:00:00Z
date_updated: 2023-10-04T11:14:04Z
day: '23'
ddc:
- '570'
degree_awarded: PhD
department:
- _id: GradSch
- _id: AnKi
doi: 10.15479/at:ista:13081
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  date_updated: 2023-05-25T06:32:12Z
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  date_created: 2023-05-25T06:32:16Z
  date_updated: 2023-05-25T06:32:16Z
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file_date_updated: 2023-05-25T06:32:16Z
has_accepted_license: '1'
language:
- iso: eng
month: '05'
oa_version: Published Version
page: '93'
publication_identifier:
  issn:
  - 2663 - 337X
publication_status: published
publisher: Institute of Science and Technology Austria
related_material:
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    relation: part_of_dissertation
    status: public
  - id: '12837'
    relation: part_of_dissertation
    status: public
status: public
supervisor:
- first_name: Anna
  full_name: Kicheva, Anna
  id: 3959A2A0-F248-11E8-B48F-1D18A9856A87
  last_name: Kicheva
  orcid: 0000-0003-4509-4998
title: Epithelial dynamics during mouse neural tube development
tmp:
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  short: CC BY-NC-ND (4.0)
type: dissertation
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year: '2023'
...