Atonal and EGFR signalling orchestraterok- andDrak-dependent adherens junction remodelling during ommatidia morphogenesis

Abstract

SUMMARYMorphogenesis of epithelial tissues relies on the interplay between cell division, differentiation and regulated changes in cell shape, intercalation and sorting. These processes are often studied individually in relatively simple epithelia that lack the complexity found during organogenesis when these processes might all coexist simultaneously. To address this issue, we are making use of the developing fly retinal neuroepithelium. Retinal morphogenesis relies on a coordinated sequence of interdependent morphogenetic events that includes apical cell constriction, localized alignment of groups of cells and ommatidia morphogenesis coupled to neurogenesis. Here, we use live imaging to document the sequence of adherens junction (AJ) remodelling events required to generate the fly ommatidium. In this context, we demonstrate that the kinases Rok and Drak function redundantly during Myosin II-dependent cell constriction, subsequent multicellular alignment and AJ remodelling. In addition, we show that early multicellular patterning characterized by cell alignment is promoted by the conserved transcription factor Atonal (Ato). Further ommatidium patterning requires the epidermal growth factor receptor (EGFR) signalling pathway, which transcriptionally governs rok-and Drakdependent AJ remodelling while also promoting neurogenesis. In conclusion, our work reveals an important role for Drak in regulating AJ remodelling during retinal morphogenesis. It also sheds new light on the interplay between Ato, EGFR-dependent transcription and AJ remodelling in a system in which neurogenesis is coupled with cell shape changes and regulated steps of cell intercalation.

The roles and regulation of multicellular rosette structures during morphogenesis

“…Similar to rosette formation in other contexts, rosette formation in the Drosophila eye disc is myosin-II dependent; rosettes and their precursors (arcs) are completely lost following overexpression of dominant-negative myosin-II heavy chain (Escudero et al, 2007;Robertson et al, 2012). Activated myosin-II is first enriched at the posterior AJs of aligned cells, prior to arc/rosette formation.…”

“…4) (Brown et al, 2006;Escudero et al, 2007;Robertson et al, 2012). These lines evolve into arcs, which are composed of six to seven cells surrounding the 'core' cells that are eventually excluded from the rosette.…”

“…During this period, markers of neuronal maturation are detectable in presumptive photoreceptors (Brown et al, 2006). Over time, core cells are excluded, progressively giving rise to a six-cell intermediate and then a five-cell rosette (Robertson et al, 2012).…”

“…In the absence of three-dimensional reconstruction studies, it is difficult to determine whether rosette formation in the Drosophila eye is based on apical or planar polarized constriction, although the localization of Par-3 and myosin-II to reciprocal domains prior to rosette formation implies a planar polarity-based mechanism (Robertson et al, 2012). Similar to rosette formation in other contexts, rosette formation in the Drosophila eye disc is myosin-II dependent; rosettes and their precursors (arcs) are completely lost following overexpression of dominant-negative myosin-II heavy chain (Escudero et al, 2007;Robertson et al, 2012).…”

“…Activated myosin-II is first enriched at the posterior AJs of aligned cells, prior to arc/rosette formation. As rosettes form, myosin-II remains localized at the outer rosette membranes, but is also present in the rosette center (Escudero et al, 2007;Robertson et al, 2012). By contrast, E-cadherin and Par-3 are enriched in the mediolateral AJs, perpendicular to posterior AJs.…”