Ssdp influences Wg expression and embryonic somatic muscle identity in Drosophila melanogaster

The somatic muscles of the Drosophila embryo and larvae share structural and functional similarities with vertebrate skeletal muscles and serve as a powerful model for studying muscle development. Here we show that the evolutionarily conserved Ssdp protein is required for the correct patterning of somatic muscles. Ssdp is part of the conserved Chi/LDB-Ssdp (ChiLS) complex that is a core component of the conserved Wg/Wnt enhanceosome, which responds to Wg signals to regulate gene transcription. Ssdp shows isoform specific expression in developing somatic muscles and its loss of function leads to an aberrant somatic muscle pattern due to a deregulated muscle identity program. Ssdp mutant embryos fail to maintain adequate expression levels of muscle identity transcription factors and this results in aberrant muscle morphology, innervation, attachment and fusion. We also show that the epidermal expression of Wg is downregulated in Ssdp mutants and that Ssdp interacts with Wg to regulate the properties of a subset of ventral muscles. Thus, our data unveil the dual contribution of Ssdp to muscle diversification by regulating the expression of muscle-intrinsic identity genes and by interacting with the extrinsic factor, Wg. The knowledge gained here about Ssdp and its interaction with Wg could be relevant to vertebrate muscle development.

Glucocorticoid-dependent transcription in skin requires epidermal expression of the glucocorticoid receptor and is modulated by the mineralocorticoid receptor

Glucocorticoid (GC) actions are mediated through two closely related ligand-dependent transcription factors, the GC receptor (GR) and the mineralocorticoid receptor (MR). Given the wide and effective use of GCs to combat skin inflammatory diseases, it is important to understand the relative contribution of these receptors to the transcriptional response to topical GCs. We evaluated the gene expression profiles in the skin of mice with epidermal-specific loss of GR (GREKO), MR (MREKO), or both (double KO; DKO) in response to dexamethasone (Dex). The overall transcriptional response was abolished in GREKO and DKO skin suggesting dependence of the underlying dermis on the presence of epidermal GR. Indeed, the observed dermal GC resistance correlated with a constitutive decrease in GR activity and up-regulation of p38 activity in this skin compartment. Upon Dex treatment, more than 90% of differentially expressed genes (DEGs) in CO overlapped with MREKO. However, the number of DEGs was fourfold increased and the magnitude of response was higher in MREKO vs CO, affecting both gene induction and repression. Taken together our data reveal that, in the cutaneous transcriptional response to GCs mediated through endogenous receptors, epidermal GR is mandatory while epidermal MR acts as a chief modulator of gene expression.