Basement membrane mechanics shape development: Lessons from the fly

Abstract

Basement membrane plays a foundational role in the structure and maintenance of many tissues throughout the animal kingdom. In addition to signaling to cells through cell-surface receptors, basement membrane directly influences the development and maintenance of organ shape via its mechanical properties. The mechanical properties of basement membrane are dictated by its composition, geometry, and crosslinking. Distinguishing between the ways the basement membrane influences morphology in vivo poses a major challenge. Drosophila melanogaster, already established as a powerful model for the analysis of cell signaling, has in recent years emerged as a tractable model for understanding the roles of basement membrane stiffness in vivo, in shaping and maintaining the morphology of tissues and organs. In addition to the plethora of genetic tools available in flies, the major proteins found in vertebrate basement membranes are all present in Drosophila. Furthermore, Drosophila has fewer copies of the genes encoding these proteins, making flies more amenable to genetic manipulation than vertebrate models. Because the development of Drosophila organs has been well-characterized, these different organ systems offer a variety of contexts for analyzing the role of basement membrane in development. The developing egg chamber and central nervous system, for example, have been important models for assessing the role of basement membrane stiffness in influencing organ shape. Studies in the nervous system have also shown how basement membrane stiffness can influence cellular migration in vivo. Finally, work in the imaginal wing disc has illuminated a distinct mechanism by which basement membrane can alter organ shape and size, by sequestering signaling ligands. This mini-review highlights the recent discoveries pertaining to basement membrane mechanics during Drosophila development.

Figure 1. Cellular sources of basement membrane in Drosophila

Basement membrane is synthesized and secreted from several different types of cells during Drosophila development. A) In developing egg chambers, follicle cells (blue) secrete their own basement membrane (green) during egg chamber elongation. B) During embryogenesis, hemocytes (blue) secrete basement membrane (green) onto developing organs, such as the ventral nerve cord (purple). C) In larvae, the fat body (yellow) secretes basement membrane proteins (green) into the open circulatory system, which are then deposited onto tissues throughout the body including the central nervous system (purple).

Figure 2. Basement membrane stiffness alters organ shape

All Drosophila organs are surrounded by a continuous sheet of basement membrane. A) The basement membrane surrounding wild-type developing egg chambers does not have uniform stiffness, but rather is more stiff in the middle and less stiff toward the poles. Perturbations that decrease the stiffness lead to rounded egg chambers, whereas those that increase the stiffness leads to hyper-elongated egg chambers. See text for details. B) The larval central nervous system is composed of two brain lobes (top) and an elongated ventral nerve cord. Perturbations that soften the basement membrane allow hyper-elongation of the ventral nerve cord, whereas those that generate stiffer basement membrane result in compaction of the ventral nerve cord and mobilize neural progenitor cells to migrate out of the central nervous system, as described in the text. C) The larval wing disc is the precursor of adult wing and notum tissues, and it has a characteristic shape. Softer basement membrane allows the wing disc to expand and flatten, whereas stiffer basement membrane compresses it, as described in the text.