RT Journal Article
SR Electronic
T1 Epithelial invagination by vertical telescoping
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 515981
DO 10.1101/515981
A1 Jingjing Li
A1 Andrew D. Economou
A1 Jeremy B.A. Green
YR 2019
UL http://biorxiv.org/content/early/2019/01/09/515981.abstract
AB Epithelial bending is a fundamental process that shapes organs during development. All currently known mechanisms involve cells locally changing shape from columnar to wedge-shaped. Often this shape change occurs by cytoskeletal contraction at cell apices (“apical constriction”) but mechanisms such as basal nuclear positioning (“basal wedging”) or extrinsic compression are also known. Here we demonstrate a completely different mechanism which occurs without cell wedging. In mammalian salivary glands and teeth, we show that initial invagination occurs through coordinated vertical cell movement. Specifically, we show that cells towards the periphery of the placode move vertically upwards while their more central neighbours move downwards to create the invagination. We further show that this occurs by active cell-on-cell migration: outer cells migrate with an apical leading edge protrusion, depressing the central cells to “telescope” the epithelium downwards into the underlaying mesenchyme. Cells remain basally attached to the underlying lamina while their apical protrusions are dynamic and planar polarised centripetally. These protrusions depend on the actin cytoskeleton, and inhibition of the branching molecule Arp2/3 inhibits them and the invagination. FGF and Hedgehog morphogen signals are also required, with FGF providing a directional cue. These findings show that epithelial bending can be achieved by novel morphogenetic mechanism of coordinated cell rearrangement quite distinct from previously recognised invagination processes.