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Biology subjects

Doumpas, N.

Publications and source records attributed to Doumpas, N..

2 recordsLinked to original sources

The emergence of the fractal bronchial tree

The fractal design of the bronchial tree, as described by the Hess-Murray law, facilitates energy-efficient lung ventilation, yet its developmental origins remain unclear. Here, we quantify the rearrangement of the embryonic bronchial tree into its fractal architecture, using SkelePlex, a new neural network-based image processing pipeline, and elucidate the biophysical principles governing its formation. We find that the branch shapes are such that pressure drop, shear, axial and hoop stress are equal across all branches. The seemingly random diameter of sister branches reflects the different number of tips they connect to in the asymmetric lung tree. By analysing lungs after pneumonectomy and those affected by chronic obstructive pulmonary disease (COPD), we show the same principles to persist in adulthood and disease, potentially providing quantitative biomarkers for disease progression and therapeutic guidance.

developmental biology↗

TBX3 acts as tissue-specific component of the Wnt/β-catenin enhanceosome

BCL9 and PYGO are {beta}-catenin cofactors that enhance the transcription of Wnt target genes. They have been proposed as therapeutic targets to diminish Wnt signalling output in intestinal malignancies. Here we find that, in colorectal cancer cells and in developing mouse forelimbs, BCL9 proteins sustain the action of {beta}-catenin in a largely PYGO-independent manner. Our genetic analyses implied that BCL9 necessitates other interaction partners in mediating its transcriptional output. We identified the transcription factor TBX3 as a candidate tissue-specific member of the {beta}-catenin transcriptional complex. In developing forelimbs, TBX3 and BCL9 co-occupy a large number of Wnt-responsive regulatory elements, genome-wide. Moreover, mutations in Bcl9 affect the expression of TBX3 targets in vivo, and modulation of TBX3 abundance impacts on Wnt target genes transcription in a {beta}-catenin- and TCF/LEF-dependent manner. Finally, TBX3 overexpression exacerbates the metastatic potential of Wnt-dependent human colorectal cancer cells. Our work implicates TBX3 as a new, context-dependent component of the Wnt/{beta}-catenin-dependent enhanceosome.

developmental biology↗