Statistical theory of branching morphogenesis.


Type
Article
Change log
Authors
Hannezo, Edouard 
Abstract

Branching morphogenesis remains a subject of abiding interest. Although much is known about the gene regulatory programs and signaling pathways that operate at the cellular scale, it has remained unclear how the macroscopic features of branched organs, including their size, network topology and spatial patterning, are encoded. Lately, it has been proposed that, these features can be explained quantitatively in several organs within a single unifying framework. Based on large-scale organ reconstructions and cell lineage tracing, it has been argued that morphogenesis follows from the collective dynamics of sublineage-restricted self-renewing progenitor cells, localized at ductal tips, that act cooperatively to drive a serial process of ductal elongation and stochastic tip bifurcation. By correlating differentiation or cell cycle exit with proximity to maturing ducts, this dynamic results in the specification of a complex network of defined density and statistical organization. These results suggest that, for several mammalian tissues, branched epithelial structures develop as a self-organized process, reliant upon a strikingly simple, but generic, set of local rules, without recourse to a rigid and deterministic sequence of genetically programmed events. Here, we review the basis of these findings and discuss their implications.

Description
Keywords
biophysical concepts, mammary gland, morphogenesis, statistical model, stem cell, Animals, Cell Lineage, Cell Proliferation, Epithelial Cells, Epithelium, Humans, Kidney, Models, Biological, Morphogenesis, Pancreas
Journal Title
Dev Growth Differ
Conference Name
Journal ISSN
0012-1592
1440-169X
Volume Title
60
Publisher
Wiley
Sponsorship
Wellcome Trust (098357/Z/12/Z)
Medical Research Council (MC_PC_12009)
Wellcome Trust (092096/Z/10/Z)
Cancer Research Uk (None)
Wellcome Trust