The control of branching morphogenesis

Abstract

Many organs of higher organisms are heavily branched structures and arise by an apparently similar process of branching morphogenesis. Yet the regulatory components and local interactions that have been identified differ greatly in these organs. It is an open question whether the regulatory processes work according to a common principle and how far physical and geometrical constraints determine the branching process. Here, we review the known regulatory factors and physical constraints in lung, kidney, pancreas, prostate, mammary gland and salivary gland branching morphogenesis, and describe the models that have been formulated to analyse their impacts.

RETRACTED: Btbd7 is essential for region-specific epithelial cell dynamics and branching morphogenesis in vivo

“…This complex, highly dynamic process remodels a simple epithelial bud into a highly arborized branched organ structure that maximizes epithelial surface area for secretion or absorption. Although many studies have highlighted requirements for numerous signaling molecules and transcription factors during branching morphogenesis (Costantini and Kopan, 2010;Harunaga et al, 2011;Hauser and Hoffman, 2015;Hennighausen and Robinson, 2005;Iber and Menshykau, 2013;Kwon and Larsen, 2015;Shih et al, 2013;Varner and Nelson, 2014), it is not fully understood at the cell and tissue level how such diverse regulatory pathways orchestrate the extensive physical remodeling that shapes branched epithelial tissues. Recent advances in microscopy have established that specific dynamic cell behaviors, such as changes in cell motility, cell-cell adhesion and cell-extracellular matrix interactions, are key functional mediators of this tissue reorganization (Daley and Yamada, 2013;Friedl and Gilmour, 2009;Harunaga et al, 2011;Huebner and Ewald, 2014;Kim and Nelson, 2012;Nelson and Larsen, 2015;Varner and Nelson, 2014).…”

A three-step framework for programming pattern formation

“…First, looking at some of the natural examples we presented in the introduction, it is evident that identical molecules are shared across mechanisms. Secondly, some mechanisms have been associated with identical morphological events, such as RBM and TPs in branching events (see [54] for a discussion). Therefore some have suggested that patterning mechanisms do not act alone but that hybrid mechanisms are more likely to be actually found in nature [55].…”

Growth, ageing and scaling laws of coronary arterial trees

“…In the derivation of scaling law, we used only the assumption of the self-similar fractal-like branching pattern [33] given cardiovascular trees have fractal-like features [34 -38]. The self-similar fractal-like branching pattern owing to diffusion-limited aggregation [21][22][23] obeys the 3/4 intraspecific length-volume scaling law, which appears to be the basic mechanism that guides the growth and ageing of coronary arterial trees. We also resolved the controversial spacefilling assumption [39,40] using the fractal axiom that LR ¼ BR À1=ð3ÀgÞ (BR and LR are the branching ratio and length ratio, respectively, as shown in appendix A).…”

“…This is the first study, to the best of our knowledge, to find an age-independent 3/4 exponent, but age-dependent scaling coefficients in the length-volume scaling law. The self-similar fractal-like branching pattern [33] owing to diffusion-limited aggregation [21][22][23] is found to be the basic mechanism for the constant 3/4 exponent. The changes of scaling coefficient have a similar trend to those of vascular resistance, both of which are attributed to the inconsistent growth/ageing rate of crown length and volume.…”

“…represents the self-similar fractal-like branching pattern under physical and biological constraints relevant to diffusion-limited aggregation [21][22][23]. Hence, although the scaling of morphology or pattern of the vascular tree is maintained throughout normal growth and ageing, the absolute size changes.…”