The laboratory mouse is a key animal model for studies of adipose biology, metabolism and disease, yet the developmental changes that occur in tissues and cells that become the adipose layer in mouse skin have received little attention. Moreover, the terminology around this adipose body is often confusing, as frequently no distinction is made between adipose tissue within the skin, and so called subcutaneous fat. Here adipocyte development in mouse dorsal skin was investigated from before birth to the end of the first hair follicle growth cycle. Using Oil Red O staining, immunohistochemistry, quantitative RT-PCR and TUNEL staining we confirmed previous observations of a close spatio-temporal link between hair follicle development and the process of adipogenesis. However, unlike previous studies, we observed that the skin adipose layer was created from cells within the lower dermis. By day 16 of embryonic development (e16) the lower dermis was demarcated from the upper dermal layer, and commitment to adipogenesis in the lower dermis was signalled by expression of FABP4, a marker of adipocyte differentiation. In mature mice the skin adipose layer is separated from underlying subcutaneous adipose tissue by the panniculus carnosus. We observed that the skin adipose tissue did not combine or intermix with subcutaneous adipose tissue at any developmental time point. By transplanting skin isolated from e14.5 mice (prior to the start of adipogenesis), under the kidney capsule of adult mice, we showed that skin adipose tissue develops independently and without influence from subcutaneous depots. This study has reinforced the developmental link between hair follicles and skin adipocyte biology. We argue that because skin adipocytes develop from cells within the dermis and independently from subcutaneous adipose tissue, that it is accurately termed dermal adipose tissue and that, in laboratory mice at least, it represents a separate adipose depot.

It is well documented that adipogenic differentiation of the cell is associated with downregulation of Wnt/β-catenin signalling. Using preadipocytes and dermal fibroblasts, we have found that activation of the adipogenic program was associated with marked changes in the expression of nuclear β-catenininteracting partners, emerin and lamins A/C, to influence expression and activation of peroxisome proliferators-activated receptors γ (PPARγ). In addition, silencing of protein expression with siRNA revealed that β-catenin and emerin influenced each other's levels of expression and the onset of adipogenesis, suggesting that changes in the expression of nuclear lamina proteins were intimately linked to the stability of β-catenin. By contrast, dermal fibroblasts, which are emerin null, demonstrated increased nuclear accumulation of stable β-catenin and constant lamin expression. This was also associated with an unusual adipogenic capacity of the cells, with adipogenesis occurring in the presence of activated β-catenin but declining upon silencing of the protein expression with siRNA. We propose that the process of adipogenesis is affected by a dynamic link between complexes of emerin and lamins A/C at the nuclear envelope and nucleocytoplasmic distribution of β-catenin, to influence cellular plasticity and differentiation.

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