Desmoplakin is required for epidermal integrity and morphogenesis in the Xenopus laevis embryo

Abstract

Desmoplakin (Dsp) is a unique and critical desmosomal protein, however, it is unclear whether this protein and desmosomes themselves are required for epidermal morphogenesis. Using morpholinos or Crispr/Cas9 mutagenesis we decreased the function of Dsp in frog embryos to better understand its role during epidermal development. Dsp morphant and mutant embryos had developmental defects that mimicked what has been reported in mammals. Such defects included epidermal fragility which correlated with reduction in cortical keratin and junctional e-cadherin in the developing epidermis. Dsp protein sequence and expression are also highly similar with mammals and suggest shared function across vertebrates. Most importantly, we also uncovered a novel function for Dsp in the morphogenesis of the epidermis in X. laevis. Specifically, Dsp is required during the process of radial intercalation where basally located cells move into the outer epidermal layer. Once inserted these newly intercalated cells expand their apical surface and then they differentiate into specific epidermal cell types. Decreased levels of Dsp resulted in the failure of the radially intercalating cells to expand their apical surface, thereby reducing the number of differentiated multiciliated and secretory cells. Dsp is also required in the development of other ectodermally derived structures such as the mouth, eye and fin that utilize intercalating-like cell movements. We have developed a novel system, in the frog, to demonstrate for the first time that desmosomes not only protect against mechanical stress but are also critical for epidermal morphogenesis.\n\nSummary StatementCritical desmosomal protein, desmoplakin, is required for proper distribution and levels of cytoskeletal elements and e-cadherin. Thus embryos with decreased desmoplakin have defects in epidermal integrity and morphogenesis.