Rac GTPases regulate the actin cytoskeleton to control changes in cell shape. To date, the analysis of Rac function during development has relied heavily on the use of dominant mutant isoforms. Here, we use loss-of-function mutations to show that the three Drosophila Rac genes, Rac1, Rac2 and Mtl, have overlapping functions in the control of epithelial morphogenesis, myoblast fusion, and axon growth and guidance. They are not required for the establishment of planar cell polarity, as had been suggested on the basis of studies using dominant mutant isoforms. The guanine nucleotide exchange factor, Trio, is essential for Rac function in axon growth and guidance, but not for epithelial morphogenesis or myoblast fusion. Different Rac activators thus act in different developmental processes. The specific cellular response to Rac activation may be determined more by the upstream activator than the specific Rac protein involved.

Growth, guidance and branching of axons are all essential processes for the precise wiring of the nervous system. Rho family GTPases transduce extracellular signals to regulate the actin cytoskeleton. In particular, Rac has been implicated in axon growth and guidance. Here we analyse the loss-of-function phenotypes of three Rac GTPases in Drosophila mushroom body neurons. We show that progressive loss of combined Rac1, Rac2 and Mtl activity leads first to defects in axon branching, then guidance, and finally growth. Expression of a Rac1 effector domain mutant that does not bind Pak rescues growth, partially rescues guidance, but does not rescue branching defects of Rac mutant neurons. Mosaic analysis reveals both cell autonomous and non-autonomous functions for Rac GTPases, the latter manifesting itself as a strong community effect in axon guidance and branching. These results demonstrate the central role of Rac GTPases in multiple aspects of axon development in vivo, and suggest that axon growth, guidance and branching could be controlled by differential activation of Rac signalling pathways.

The basement membrane is a highly intricate and organized portion of the extracellular matrix that interfaces with a variety of cell types including epithelial, endothelial, muscle, nerve, and fat cells. The laminin family of glycoproteins is a major constituent of the basement membrane. The 16 known laminin isoforms are formed from combinations of alpha, beta, and gamma chains, with each chain containing specific domains capable of interacting with cellular receptors such as integrins and other extracellular ligands. In addition to its role in the assembly and architectural integrity of the basement membrane, laminins interact with cells to influence proliferation, differentiation, adhesion, and migration, processes activated in normal and pathologic states. In vitro these functions are regulated by the post-translational modifications of the individual laminin chains. In vivo laminin knockout mouse studies have been particularly instructive in defining the function of specific laminins in mammalian development and have also highlighted its role as a key component of the basement membrane. In this review, we will define how laminin structure complements function and explore its role in both normal and pathologic processes.

The role of the extracellular matrix in cutaneous morphogenesis is poorly understood. Here, we describe the essential role of laminin‐10 (α5β1γ1) in hair follicle development. Laminin‐10 was present in the basement membrane of elongating hair germs, when other laminins were downregulated, suggesting a role for laminin‐10 in hair development. Treatment of human scalp xenografts with antibodies to laminin‐10, or its receptor β1 integrin, produced alopecia. E16.5 Lama5 −/− mouse skin, lacking laminin‐10, contained fewer hair germs compared with controls, and after transplantation, Lama5 −/− skin showed a failure of hair germ elongation followed by complete hair follicle regression. Lama5 −/− skin showed defective basement membrane assembly, without measurable increases in anoikis. Instead, Lama5 −/− skin showed decreased expression of early hair markers including sonic hedgehog and Gli1, implicating laminin‐10 in developmental signaling. Intriguingly, treatment of Lama5 −/− skin with purified laminin‐10 corrected basement membrane defects and restored hair follicle development. We conclude that laminin‐10 is required for hair follicle development and report the first use of exogenous protein to correct a cutaneous developmental defect.

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Dermoscopy increases the clinician's diagnostic accuracy by as much as 30% over that of unaided visual clinical inspection alone and has been confirmed in 3 separate evidence-based publications using a meta-analysis of the literature. It can be viewed as an in vivo bridge between clinical morphology and histopathology. This "bridge" has provided clinician researchers with many new insights into morphology and tumor biology. In this article, we provide the reader with an overview of the different aspects of dermoscopy as a research tool. We cover different aspects, such as the new equipment, new structures, the importance of blood vessels, etc.

Psoriasis is a chronic T-cell-mediated inflammatory disease of the skin and joints that affects 1-3% of the world population. Conventional treatments for moderate to severe psoriasis are associated with broadband immunosuppression and/or organ toxicities that can be problematic when used long term. Advances in the understanding of psoriasis pathogenesis have led to targeted therapy in the form of biologics. These agents have gained popularity as safe, effective, and convenient alternatives for the treatment of chronic, moderate to severe plaque psoriasis. This review will focus on the five main biologics used in the treatment of moderate to severe plaque psoriasis: efalizumab, alefacept, etanercept, infliximab and adalimumab. Mechanisms of action, guidelines for usage, efficacy data, and safety concerns will be discussed for each biologic. In addition, the new Th17 biologics and their role in psoriasis pathogenesis will also be examined.

Basal cell carcinoma (BCC) is the most common cutaneous malignancy that, like other tumours, possesses a heterogeneous genetic composition. In order to select genes with consistent changes in expression among these tumours, we analysed BCC microarray expression data by using a novel approach, termed correlative analysis of microarrays (CAM). CAM is a nested, non-parametric method designed to qualitatively select candidates based on their individual, similar effects upon an array-wide closeness measure. We applied the CAM method to expression data generated by two-channel cDNA microarray experiments, where 21 BCC and patient-matched normal skin specimens were examined. Fifteen candidate genes were selected, with six overexpressed and nine underexpressed in BCC vs. normal skin. Five of the nine consistently downregulated genes in the tumour samples are involved in mitochondrial function and the oxidative phosphorylation (OXPHOS) pathway. One of these genes was the 7.5-kDa subunit, NADH dehydrogenase (ubiquinone) alpha subcomplex-1 (NDUFA1), an accessory component of OXPHOS complex-I that is essential for respiratory activity. These findings support the hypothesis that irregularities in mitochondrial function are involved in neoplasia. Suppression of NDUFA1 expression could represent a key pathogenic mechanism in the development of BCC.