Dataset FigS2A_FGFinternalize
Project
398-Hirashima-LungMorpho
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
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.
Title
Time-lapse images of bright field, FGF1-Alexa488, and FGF1-pHrodo in an isolated lung epithelium embedded within the Matrigel
Description
Time-lapse images of bright field, FGF1-Alexa488, and FGF1-pHrodo in an isolated lung epithelium embedded within the Matrigel. To visualize internalized FGF1, pHrodo-labeled FGF1 and Alexa488-labeled FGF1 were added to the culture ex vivo.
Channel1; bright field, Channel2; FGF1-Alexa488, Channel3; FGF1-pHrodo
Description
Isolated epithelial tissues cultured within growth factor-reduced Matrigel.
Extrinsic variables
To visualize internalized FGF1, pHrodo-labeled FGF1 and Alexa488-labeled FGF1 were added to the culture ex vivo.
Gene ontology: Biological processes
Gene ontology: Cellular components
Gene ontology: Molecular functions
Protein names
Fibroblast growth factor 1 (
P61148)
Dimensions
800x800x1x3x120
X scales
0.397 micrometer
Y scales
0.397 micrometer
Detection methods
photodiode
Visualization methods
pHrodo
Alexa Fluor 488
Illumination methods
photodiode
Contrast enhancing methods
optical method
Resolution enhancing methods
Sample preparation methods
living tissue
Objective
XLPLN25XWMP2, Olympus