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Morphogen gradients provide essential positional information to gene networks through their spatially heterogeneous distribution, yet how they form is still hotly contested, with multiple models proposed for different systems. Here, we focus on the transcription factor Bicoid (Bcd), a morphogen that forms an exponential gradient across the anterior-posterior (AP) axis of the early Drosophila embryo. Using fluorescence correlation spectroscopy we find there are spatial differences in Bcd diffusivity along the AP axis, with Bcd diffusing more rapidly in the posterior. We establish that such spatially varying differences in Bcd dynamics are sufficient to explain how Bcd can have a steep exponential gradient in the anterior half of the embryo and yet still have an observable fraction of Bcd near the posterior pole. In the nucleus, we demonstrate that Bcd dynamics are impacted by binding to DNA. Addition of the Bcd homeodomain to eGFP::NLS qualitatively replicates the Bcd concentration profile, suggesting this domain regulates Bcd dynamics. Our results reveal how a long-range gradient can form while retaining a steep profile through much of its range. [ABSTRACT FROM AUTHOR]

During tissue closures, such as embryonic dorsal closure in Drosophila melanogaster, a proximate extra-embryonic layer, amnioserosa, generates forces that drive migration of the flanking lateral embryonic epidermis, thereby zip-shutting the embryo. Arguably, this paradigm of tissue closure is also recapitulated in mammalian wound healing wherein proximate fibroblasts transform into contractile myofibroblasts, develop cell junctions, and form a tissue layer de novo: contraction of the latter then aids in wound closure. Given this parallelism between disparate exemplars, we posit a general principle of tissue closure via proximate cell layer-generated forces. Here, we have tested this hypothesis in pupal thorax closure wherein 2 halves of the presumptive adult thorax of Drosophila, the contralateral heminotal epithelia, migrate over an underlying larval epidermal cell layer. We show that the proximate larval epidermal cell layer promotes thorax closure by its active contraction, orchestrated by its elaborate actomyosin network-driven epithelial cell dynamics, cell delamination, and death--the latter being prefigured by the activation of caspases. Larval epidermal cell dynamics generate contraction forces, which when relayed to the flanking heminota--via their mutual integrin-based adhesions--mediate thorax closure. Compromising any of these contraction forcegenerating mechanisms in the larval epidermal cell layer slows down heminotal migration, while loss of its relay to the flanking heminota abrogates the thorax closure altogether. Mathematical modeling further reconciles the biophysical underpinning of this emergent mechanism of thorax closure. Revealing mechanism of thorax closure apart, these findings show conservation of an essential principle of a proximate cell layer-driven tissue closure. [ABSTRACT FROM AUTHOR]

Spatiotemporal changes in epithelial cell sizes-or epithelial cell size dynamics (ECD)-during morphogenesis entail interplay between two opposing forces: cell contraction via actomyosin cytoskeleton and cell expansion via cell-cell adhesion. Cell-cell adhesion-based ECD, however, has not yet been clearly demonstrated. For instance, changing levels of homophilic E-cadherin-based cell-cell adhesion induce cell sorting, but not ECD. Here we show that cell-expansive forces of heterophilic cell-cell adhesion regulate ECD: higher cell-cell adhesion results in cell size enlargement. Thus, ECD during morphogenesis in the heminotal epithelia of Drosophila pupae leading to thorax closure corresponds with spatiotemporal gradients of two heterophilic atypical cadherins-Fat (Ft) and Dachsous (Ds)-and the levels of Ft-Ds heterodimers formed concomitantly. Our mathematical modeling and genetic tests validate this mechanism of dynamic heterophilic cell-cell adhesion-based regulation of ECD. Conservation of these atypical cadherins suggests a wider prevalence of heterophilic cell-cell adhesion-based ECD regulation during animal morphogenesis.