SSBD Project Detail

398-Hirashima-LungMorpho

OMERO gallery,

OMERO index

Project

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

License

CC BY

Released at

Oct. 20, 2025, midnight

Updated at

Funding

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.

# of image datasets

Papers

Paper information: Hirashima T and Matsuda M. ERK-mediated curvature feedback regulates branching morphogenesis in lung epithelial tissue. Curr Biol. 2024 Feb 26;34(4):683-696.e6.,
Pubmed ID: 38228149,
DOI: https://doi.org/10.1016/j.cub.2023.12.049,
URL: https://pubmed.ncbi.nlm.nih.gov/38228149/

Contacts

Tsuyoshi Hirashima (Contact) , Mechanobiology Institute , National University of Singapore

Biosamples

Organisms

Mus musculus (NCBI:txid10090)

Strains

hyBRET-ERK-NES
hyBRET-ERK-NES
Slc:ICR

Cells

epithelial cell of lung (CL_0000082)

Cell lines

Ontologies

UBERON

lung epithelium (UBERON_0000115)

Anatomical entities

GO: Biological processes

signal transduction (GO:0007174)
signal transduction (GO:0007175)
signal transduction (GO:0007178)
signal transduction (GO:0007173)
signal transduction (GO:0007181)
signal transduction (GO:0007169)
signal transduction (GO:0007179)
lung lobe formation (GO:0060464)
signal transduction (GO:0007171)
signal transduction (GO:0007172)
signal transduction (GO:0007166)
signal transduction (GO:0007177)
signal transduction (GO:0007168)
signal transduction (GO:0007165)
signal transduction (GO:0007176)
signal transduction (GO:0007167)
signal transduction (GO:0007180)

GO: Cellular components

cytoskeleton (GO:0005856)
cytosol (GO:0005829)

GO: Molecular functions

structural constituent of cytoskeleton (GO:0005200)

Genetics

Gene names

Protein names

Fibroblast growth factor 1 (P61148)
Actin, cytoplasmic 1 (P60710)
Cadherin-1 (P09803)

Genetic methods

transgenic (EFO_0004020)

Protein tags

Yellow fluorescent protein from Aequorea (FBbi:00000439)

Probes

antibody, Alexa Fluor 647 (FBbi:00000401)
antibody, Alexa Fluor 488 (FBbi:00000401)

Oligo Primer

Genotype

Treatments

Reagent or Compound

Concentration

Fold Dilution

FGF1-Alexa488

FGF7 (OGG:3000002252)

100 nanogram per milliliter (UO_0000275)

FGF1 (OGG:3000002246)