---
_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:10.15479/at:ista:14323
apa: Kuzmicz-Kowalska, K. (2023). Regulation of neural progenitor survival by
Shh and BMP in the developing spinal cord. Institute of Science and Technology
Austria. https://doi.org/10.15479/at:ista:14323
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. https://doi.org/10.15479/at:ista:14323.
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. Regulation of Neural Progenitor Survival by
Shh and BMP in the Developing Spinal Cord. Institute of Science and Technology
Austria, 2023, doi:10.15479/at:ista:14323.
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:
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- _id: AnKi
doi: 10.15479/at:ista:14323
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date_created: 2023-09-13T09:52:52Z
date_updated: 2023-09-13T10:08:25Z
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publisher: Institute of Science and Technology Austria
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supervisor:
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full_name: Kicheva, Anna
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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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---
_id: '7883'
abstract:
- lang: eng
text: All vertebrates have a spinal cord with dimensions and shape specific to their
species. Yet how species‐specific organ size and shape are achieved is a fundamental
unresolved question in biology. The formation and sculpting of organs begins during
embryonic development. As it develops, the spinal cord extends in anterior–posterior
direction in synchrony with the overall growth of the body. The dorsoventral (DV)
and apicobasal lengths of the spinal cord neuroepithelium also change, while at
the same time a characteristic pattern of neural progenitor subtypes along the
DV axis is established and elaborated. At the basis of these changes in tissue
size and shape are biophysical determinants, such as the change in cell number,
cell size and shape, and anisotropic tissue growth. These processes are controlled
by global tissue‐scale regulators, such as morphogen signaling gradients as well
as mechanical forces. Current challenges in the field are to uncover how these
tissue‐scale regulatory mechanisms are translated to the cellular and molecular
level, and how regulation of distinct cellular processes gives rise to an overall
defined size. Addressing these questions will help not only to achieve a better
understanding of how size is controlled, but also of how tissue size is coordinated
with the specification of pattern.
acknowledgement: 'Austrian Academy of Sciences, Grant/Award Number: DOC fellowship
for Katarzyna Kuzmicz-Kowalska; Austrian Science Fund, Grant/Award Number: F78 (Stem
Cell Modulation); H2020 European Research Council, Grant/Award Number: 680037'
article_number: e383
article_processing_charge: Yes (via OA deal)
article_type: original
author:
- first_name: Katarzyna
full_name: Kuzmicz-Kowalska, Katarzyna
id: 4CED352A-F248-11E8-B48F-1D18A9856A87
last_name: Kuzmicz-Kowalska
- first_name: Anna
full_name: Kicheva, Anna
id: 3959A2A0-F248-11E8-B48F-1D18A9856A87
last_name: Kicheva
orcid: 0000-0003-4509-4998
citation:
ama: 'Kuzmicz-Kowalska K, Kicheva A. Regulation of size and scale in vertebrate
spinal cord development. Wiley Interdisciplinary Reviews: Developmental Biology.
2021. doi:10.1002/wdev.383'
apa: 'Kuzmicz-Kowalska, K., & Kicheva, A. (2021). Regulation of size and scale
in vertebrate spinal cord development. Wiley Interdisciplinary Reviews: Developmental
Biology. Wiley. https://doi.org/10.1002/wdev.383'
chicago: 'Kuzmicz-Kowalska, Katarzyna, and Anna Kicheva. “Regulation of Size and
Scale in Vertebrate Spinal Cord Development.” Wiley Interdisciplinary Reviews:
Developmental Biology. Wiley, 2021. https://doi.org/10.1002/wdev.383.'
ieee: 'K. Kuzmicz-Kowalska and A. Kicheva, “Regulation of size and scale in vertebrate
spinal cord development,” Wiley Interdisciplinary Reviews: Developmental Biology.
Wiley, 2021.'
ista: 'Kuzmicz-Kowalska K, Kicheva A. 2021. Regulation of size and scale in vertebrate
spinal cord development. Wiley Interdisciplinary Reviews: Developmental Biology.,
e383.'
mla: 'Kuzmicz-Kowalska, Katarzyna, and Anna Kicheva. “Regulation of Size and Scale
in Vertebrate Spinal Cord Development.” Wiley Interdisciplinary Reviews: Developmental
Biology, e383, Wiley, 2021, doi:10.1002/wdev.383.'
short: 'K. Kuzmicz-Kowalska, A. Kicheva, Wiley Interdisciplinary Reviews: Developmental
Biology (2021).'
date_created: 2020-05-24T22:01:00Z
date_published: 2021-04-15T00:00:00Z
date_updated: 2024-03-07T15:03:00Z
day: '15'
ddc:
- '570'
department:
- _id: AnKi
doi: 10.1002/wdev.383
ec_funded: 1
external_id:
isi:
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creator: dernst
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date_updated: 2020-11-24T13:11:39Z
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month: '04'
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oa_version: Published Version
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project:
- _id: B6FC0238-B512-11E9-945C-1524E6697425
call_identifier: H2020
grant_number: '680037'
name: Coordination of Patterning And Growth In the Spinal Cord
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name: The role of morphogens in the regulation of neural tube growth
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grant_number: F07802
name: Morphogen control of growth and pattern in the spinal cord
publication: 'Wiley Interdisciplinary Reviews: Developmental Biology'
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issn:
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publication_status: published
publisher: Wiley
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scopus_import: '1'
status: public
title: Regulation of size and scale in vertebrate spinal cord development
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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: 3E5EF7F0-F248-11E8-B48F-1D18A9856A87
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...