Epiboly generates the epidermal basal monolayer and spreads the nascent mammalian skin to enclose the embryonic body

Abstract

Epiboly is a morphogenetic process that is employed in the surface ectoderm of anamniotes during gastrulation to cover the entire embryo. We propose here that mammals also utilise this process to expand the epidermis and enclose the body cavity and spinal cord with a protective surface covering. Our data supports a model whereby epidermal spreading is driven by the primary establishment of the epidermal basal progenitor monolayer through radial cell intercalation of a multi-layered epithelium towards the basal lamina. By using a suspension organotypic culture strategy, we find that this process is fibronectin-dependent and autonomous to the skin. The radial cell rearrangements that drive epidermal spreading also require ROCK activity but are driven by cell protrusions and not myosin II contractility. Epidermal progenitor monolayer formation and epidermal spreading are delayed in Crash mice, which possess a dominant mutation in Celsr1, an orthologue of the core planar cell polarity (PCP) Drosophila protein Flamingo (also known as Stan). We observe a failure of ventral enclosure in Crash mutants suggesting that defective epidermal spreading might underlie some ventral wall birth defects.

The Physical Basis of Coordinated Tissue Spreading in Zebrafish Gastrulation

“…In Xenopus gastrulation, for instance, the blastocoel roof spreads by radial intercalation of deep cells on the basal side of the overlying superficial epithelial cells, which in turn undergo pronounced expansion (Keller, 1978). Likewise in mouse embryogenesis, epidermal spreading has recently been associated with expansion of superficial cells and radial intercalation of deep cells (Panousopoulou et al., 2016). Yet, how surface cell expansion and radial deep cell intercalation function together to trigger tissue spreading remains unclear.…”

The role of Rho kinase (Rock) in re-epithelialization of adult zebrafish skin wounds

“…Interestingly, a recent report suggests that ROCK functions downstream of the PCP component Celsr1 during mouse epidermal radial intercalations but that this signaling axis may be separate from other PCP driven developmental processes. 41 Collectively, our data indicate that the coupling of basal/intermediary radial intercalation and cell flattening and elongation, both reliant on Rock function, within the following keratinocytes is vital for, and is likely to be the driving force behind, the rapid re-epithelialization characteristic of adult zebrafish. In contrast, the PCP- and Rock-dependent directionality of cell elongations only has a minor impact on wound re-epithelialization, possibly by indirectly promoting radial cell intercalations that would be compromised if cells elongated in random directions.…”

Resolving morphogenesis into quantifiable cell behaviours

“…CE is widespread in development. Elongation and narrowing of kidney tubules ( Lienkamp et al, 2012 ), the cochlea of the inner ear ( Montcouquiol and Kelley, 2020 ), the cartilage of the jaw ( Rochard et al, 2015 ), the invagination of the molar tooth bud ( Panousopoulou et al, 2016 ), the Drosophila hindgut ( Iwaki et al, 2001 ) and the long bone growth zones ( Li and Dudley, 2009 ) are just some examples. CE uses the Wnt planar cell polarity pathway, which is required for the orientation of cell protrusiveness, i.e.…”

“…It drives the early development of zebrafish, when the embryo spreads down and around the yolk, and wraps the ectoderm (prospective epidermis and neuroepithelium) around the other germ layers ( Bruce and Heisenberg, 2020 ). Epiboly also occurs in other contexts, for example in ventral closure in mammals ( Panousopoulou et al, 2016 ) and in wound healing ( Diegelmann and Evans, 2004 ).…”