Rapid Expansion of Embryonic Epithelia Requires Extensive Basement Membrane Perforation

Wednesday, October 10, 2012 — Poster Session II
Noon – 2:00 p.m	Natcher Conference Center, Building 45	NIDCR	DEV-5

* FARE Award Winner

Authors

• J.S. Harunaga
• A.D. Doyle
• M.A. Conti
• R.S. Adelstein
• K.M. Yamada

Abstract

Branched organs such as lung, kidney, and salivary glands undergo rapid epithelial expansion during development to generate the maximal surface area needed for adsorption or secretion. While many have investigated how cells invade through a basement membrane (BM) in pathological processes, the fundamental question of how embryonic epithelia normally expand rapidly while remaining confined by the BM is poorly understood. We hypothesized that the BM must be weakened at sites of high expansion to permit outgrowth. To investigate this, we imaged several BM components of ex vivo embryonic mouse lung and submandibular gland and observed extensive tiny perforations in the BM around the tips of rapidly expanding end buds, yet the perforations are absent around ducts where there is little expansion. These perforations give the usually continuous, stiff BM a mesh-like quality, likely increasing its elasticity to permit expansion. The perforations increase in number and size with epithelial expansion and gradually disappear as expansion slows. Protease or non-muscle myosin II inhibition resulted in a buildup of BM, disappearance of perforations, and significant inhibition of outgrowth. In summary, we have discovered a new mechanism facilitating epithelial expansion associated with mechanical and proteolytic remodeling of the BM necessary for organ development.

back to top