Myosin Vb mediated plasma membrane homeostasis regulates peridermal cell size and maintains tissue homeostasis in the zebrafish epidermis.

The epidermis is a stratified epithelium, which forms a barrier to maintain the internal milieu in metazoans. Being the outermost tissue, growth of the epidermis has to be strictly coordinated with the growth of the embryo. The key parameters that determine tissue growth are cell number and cell size. So far, it has remained unclear how the size of epidermal cells is maintained and whether it contributes towards epidermal homeostasis. We have used genetic analysis in combination with cellular imaging to show that zebrafish goosepimples/myosin Vb regulates plasma membrane homeostasis and is involved in maintenance of cell size in the periderm, the outermost epidermal layer. The decrease in peridermal cell size in Myosin Vb deficient embryos is compensated by an increase in cell number whereas decrease in cell number results in the expansion of peridermal cells, which requires myosin Vb (myoVb) function. Inhibition of cell proliferation as well as cell size expansion results in increased lethality in larval stages suggesting that this two-way compensatory mechanism is essential for growing larvae. Our analyses unravel the importance of Myosin Vb dependent cell size regulation in epidermal homeostasis and demonstrate that the epidermis has the ability to maintain a dynamic balance between cell size and cell number.

Zebrafish twist2/dermo1 regulates scale shape and scale organization during skin development and regeneration.

Scales are skin appendages in fishes that evolutionarily predate feathers in birds and hair in mammals. Zebrafish scales are dermal in origin and develop during metamorphosis. Understanding regulation of scale development in zebrafish offers an exciting possibility of unraveling how the mechanisms of skin appendage formation evolved in lower vertebrates and whether these mechanisms remained conserved in birds and mammals. Here we have investigated the expression and function of twist 2/dermo1 gene - known for its function in feather and hair formation - in scale development and regeneration. We show that of the four zebrafish twist paralogues, twist2/dermo1 and twist3 are expressed in the scale forming cells during scale development. Their expression is also upregulated during scale regeneration. Our knockout analysis reveals that twist2/dermo1 gene functions in the maintenance of the scale shape and organization during development as well as regeneration. We further show that the expression of twist2/dermo1 and twist3 is regulated by Wnt signaling. Our results demonstrate that the function of twist2/dermo1 in skin appendage formation, presumably under regulation of Wnt signaling, originated during evolution of basal vertebrates.

Zebrafish penner/lethal giant larvae 2 functions in hemidesmosome formation, maintenance of cellular morphology and growth regulation in the developing basal epidermis.

Epithelial cells are equipped with junctional complexes that are involved in maintaining tissue architecture, providing mechanical integrity and suppressing tumour formation as well as invasiveness. A strict spatial segregation of these junctional complexes leads to the polarisation of epithelial cells. In vertebrate epithelia, basally localised hemidesmosomes mediate stable adhesion between epithelial cells and the underlying basement membrane. Although components of hemidesmosomes are relatively well known, the molecular machinery involved in governing the formation of these robust junctions, remains elusive. Here, we have identified the first component of this machinery using a forward genetic approach in zebrafish as we show that the function of penner (pen)/lethal giant larvae 2 (lgl2) is necessary for hemidesmosome formation and maintenance of the tissue integrity in the developing basal epidermis. Moreover, in pen/lgl2 mutant, basal epidermal cells hyper-proliferate and migrate to ectopic positions. Of the two vertebrate orthologues of the Drosophila tumour suppressor gene lethal giant larvae, the function of lgl2 in vertebrate development and organogenesis remained unclear so far. Here, we have unravelled an essential function of lgl2 during development of the epidermis in vertebrates.