Unit Operations of Tissue Development: Epithelial Folding

Abstract

The development of multicellular organisms relies on a small set of construction techniques—assembly, sculpting, and folding—that are spatially and temporally regulated in a combinatorial manner to produce the diversity of tissues within the body. These basic processes are well conserved across tissue types and species at the level of both genes and mechanisms. Here we review the signaling, patterning, and biomechanical transformations that occur in two well-studied model systems of epithelial folding to illustrate both the complexity and modularity of tissue development. In particular, we discuss the possibility of a spatial code specifying morphogenesis. To decipher this code, engineers and scientists need to establish quantitative experimental systems and to develop models that address mechanisms at multiple levels of organization, from gene sequence to tissue biomechanics. In turn, quantitative models of embryogenesis can inspire novel methods for creating synthetic organs and treating degenerative tissue diseases.

Differential lateral and basal tension drive folding of Drosophila wing discs through two distinct mechanisms

“…Epithelial sheets adopt complex three-dimensional shapes through a sequence of folding steps during animal development 1 – 3 . Epithelial folding is instrumental during processes such as embryonic gastrulation 4 and neural tube 5 and eye 6 formation, and defects in epithelial folding can lead to severe developmental disorders in humans 7 .…”

Epithelial Patterning, Morphogenesis, and Evolution: Drosophila Eggshell as a Model

“…Epithelial morphogenesis is similar to origami (Zartman and Shvartsman, 2010), since in both processes a two-dimensional sheet (of cells, or paper) is patterned (with gene-expression patterns, or folds) to guide its transformation into a 3D structure. However, epithelial morphogenesis is clearly more complex.…”

Distinct shape-shifting regimes of bowl-shaped cell sheets – embryonic inversion in the multicellular green alga Pleodorina

“…The interaction of self-deforming, connected cells results in a global three-dimensional shape-shifting of a cell sheet or tissue. However, cell sheet folding in animal model organisms frequently involves other processes such as cell division, migration and intercalation, which obscure the specific role of cell shape changes [ 62 – 67 , 70 – 80 ].…”