398-Hirashima-LungMorpho
Author reviewedSpatio-temporal activation of ERK during branching morphogenesis in lung
Project ID
398-Hirashima-LungMorpho
Project SID
398
Title
Spatio-temporal activation of ERK during branching morphogenesis in lung
Description
Intricate branching patterns emerge in internal organs due to the recurrent occurrence of simple deformations in epithelial tissues. During murine lung development, epithelial cells in distal tips of the single tube require fibroblast growth factor (FGF) signals emanating from their surrounding mesenchyme to form repetitive tip bifurcations. However, it remains unknown how the cells employ FGF signaling to convert their behaviors to achieve the recursive branching processes. Here, the authors show a mechano-chemical regulatory system underlying lung branching morphogenesis, orchestrated by extracellular signal-regulated kinase (ERK) as a downstream driver of FGF signaling. They found that tissue-scale curvature regulated ERK activity in the lung epithelium using two-photon live cell imaging and mechanical perturbations. ERK activation occurs specifically in epithelial tissues exhibiting positive curvature, regardless of whether the change in curvature was attributable to morphogenesis or perturbations. Moreover, ERK activation accelerates actin polymerization preferentially at the apical side of cells, mechanically contributing to the extension of the apical membrane, culminating in a reduction of epithelial tissue curvature. These results indicate the existence of a negative feedback loop between tissue curvature and ERK activity that transcends spatial scales. Their mathematical model confirms that this regulatory mechanism is sufficient to generate the recursive branching processes. Taken together, they propose that ERK orchestrates a curvature feedback loop pivotal to the self-organized patterning of tissues.
See GitHub for code and sample images of simulations from Fig6 onwards
Submission Date
2024-11-14
Opened Date
-
Release Date
2025-02-13
Update Date
-
Kind
Image datasets
License
Project URL
-
Project DOI
-
Metadata Version
-
Template Version
-
Funding Information
This work was supported by JST PRESTO grant JPMJPR1949, JSPS KA- KENHI 19H00993 and 21H05290, the Medical Research Support Center of Kyoto University, and the Mechanobiology Institute (MBI) at the National Uni- versity of Singapore funded through the National Research Foundation, Singapore and the Ministry of Education, Singapore under the Research Centre of Excellence program and by the Department of Physiology at the Na- tional University of Singapore.
Total
1981 files / 22.9 GB
Image datasets
zipped 17 files / 8.4 GB, raw image 1964 files / 14.5 GB, total 1981 files / 22.9 GB
Quantitative datasets
zipped 0 files / 0 bytes, raw bdml 0 files / 0 bytes, total 0 files / 0 bytes
Biosample
Organism
Mus musculus
(
NCBITaxon:10090
)
Strain
hyBRET-ERK-NES
(
https://animal.nibiohn.go.jp/e_hybret-erk-nes.html
)
Slc:ICR
(
http://www.jslc.co.jp/pdf/data/2007/icr2007.pdf
)
Cell
epithelial cell of lung
(
CL:0000082
)
Cell line
-
MeSH
Ontology
Anatomical Entity
-
UBERON
lung epithelium
(
UBERON:0000115
)
Biological Process
lung lobe formation,
signal transduction,
(
GO:0007165
)
lung lobe formation,
signal transduction,
(
GO:0007166
)
lung lobe formation,
signal transduction,
(
GO:0007169
)
lung lobe formation
(
GO:0007170
)
lung lobe formation,
signal transduction,
(
GO:0007171
)
lung lobe formation,
signal transduction,
(
GO:0007172
)
lung lobe formation,
signal transduction,
(
GO:0007173
)
lung lobe formation,
signal transduction,
(
GO:0007174
)
lung lobe formation,
signal transduction,
regulation of cytoskeleton organization
(
GO:0007177
)
lung lobe formation,
signal transduction,
regulation of cytoskeleton organization
(
GO:0007179
)
lung lobe formation,
signal transduction,
regulation of cytoskeleton organization
(
GO:0007178
)
lung lobe formation,
signal transduction,
(
GO:0007167
)
lung lobe formation,
signal transduction,
(
GO:0007168
)
lung lobe formation,
signal transduction,
(
GO:0007176
)
lung lobe formation,
signal transduction,
(
GO:0007175
)
lung lobe formation,
signal transduction,
regulation of cytoskeleton organization
(
GO:0007181
)
lung lobe formation,
signal transduction,
regulation of cytoskeleton organization
(
GO:0007180
)
Cellular Component
cytosol
(
GO:0005829
)
cytosol,
cytoskeleton
(
GO:0005856
)
Molecular Function
structural constituent of cytoskeleton
(
GO:0005200
)
Medical Subject Headings
Imaging Method
Method involved in biological imaging
two-photon laser scanning microscopy
(
FBbi:00000254
)
confocal microscopy
(
FBbi:00000251
)
Paper DOI / Paper URL
People
Contact
Tsuyoshi Hirashima
National University of Singapore
Mechanobiology Institute
-
-
Imaging dataset contributor
-
Quantitative dataset contributor
-
Image datasets
17
Quantitative datasets
0
Dataset List
Thumbnail
Dataset
Organism
Kind / Links
Z-series images of ERK activity in a developing lung detected by cytoplasmic FRET biosensor for the ERK activity
Time-lapse images of ERK activity detected by FRET biosensor for the ERK activity during terminal bifurcation of an epithelium in an intact lung lobe
Time-lapse images of ERK activity during the terminal bifurcation of an isolated lung epithelium treated with FGF1
Z-series images of the whole-mount immunofluorescence of anti-E-cadherin for FGF1-treated isolated lung epithelial tissues
Time-series images of ERK activity at the tip of an isolated lung epithelium against compression parallel to the distal-proximal axis
Time-series images of ERK activity at the tip of an isolated lung epithelium against the compression vertical to the distal-proximal axis
Time-lapse images of the ERK activity in dissociated lung epithelial cells for the compression under planar culture conditions
Time-lapse images of the ERK activity in dissociated lung epithelial cells for the extension under planar culture conditions
Z-series images of ERK activity and F-actin accumulation level visualized by SiR-actin labeling upon treatment with FGF1
Time-lapse images of SiR-actin simultaneously imaged ERK activity upon treatment with FGF1
Time-lapse images of ERK activity simultaneously imaged SiR-actin upon treatment with FGF1
Time-lapse images of bright field, FGF1-Alexa488, and FGF1-pHrodo in an isolated lung epithelium embedded within the Matrigel
Time-lapse images of ERK activity during the morphological change of an isolated lung epithelium treated with FGF7
Time-lapse images of ERK activity of an isolated lung epithelium after treatment with PD0325901
Time-lapse images of ERK activity of an isolated lung epithelium before treatment with PD0325901
Time-lapse images of SiR-actin simultaneously imaged ERK activity upon treatment with FGF1 and PD0325901
Time-lapse images of ERK activity simultaneously imaged SiR-actin upon treatment with FGF1 and PD0325901