Multiscale dynamics of branching morphogenesis

Abstract

Branching morphogenesis is a prototypical example of complex three-dimensional organ sculpting, required in multiple developmental settings to maximize the area of exchange surfaces. It requires, in particular, the coordinated growth of different cell types together with complex patterning to lead to robust macroscopic outputs. In recent years, novel multiscale quantitative biology approaches, together with biophysical modelling, have begun to shed new light of this topic. Here, we wish review some of these recent developments, highlighting the generic design principles that can be abstracted across different branched organs, as well as the implications for the broader fields of stem cell, developmental and systems biology.

Mechanical Pressure Driving Proteoglycan Expression in Mammographic Density: a Self-perpetuating Cycle?

“…Mathematical models are a valuable tool to help interpret biological experiments and provide a framework to develop mechanistic understanding otherwise difficult if not impossible with experimentation alone. While many mathematical models are utilised to explore cancer development [68], mammary branching morphogenesis [69][70][71], and mechanical pressure in tissue development [72], few mathematical models have to date connected mechanical pressure, proteoglycan expression, and MD. In the following we highlight some recent biologically motivated mathematical modelling studies in the field.…”

Exploring the interdependence between self-organization and functional morphology in cellular systems

“…Indeed, mathematical modelling indicates that the optimal geometrical solution (i.e. dendritic tree shape) relies on source distribution and resorption rates (Ochoa-Espinosa and Affolter, 2012;Hannezo et al, 2017;Hannezo and Simons, 2019). For instance, absorption of slowly diffusing objects requires a denser network than for fast diffusing material.…”

Theory of branching morphogenesis by local interactions and global guidance

“…A complementary question has been to understand the dynamical mechanisms through which branching complexity can arise during development. It has been shown in particular that branching morphogenesis proceeds via tip-driven growth and/or side branching events, which are shaped by combinations of deterministic and stochastic rules [4, 18–20]. Indeed, different cellular strategies have been demonstrated to regulate the final branching pattern, from stereotypic transcription factor expression [21], stochastic local rules [22, 23], mechanical forces and local reaction-diffusion mechanisms [2, 3, 24] to epigenetic mechanisms [25] and codes of cell adhesion molecules [19, 26].…”