Irf6 is a key determinant of the keratinocyte proliferation-differentiation switch.

The epidermis is a highly organized structure, the integrity of which is central to the protection of an organism. Development and subsequent maintenance of this tissue depends critically on the intricate balance between proliferation and differentiation of a resident stem cell population; however, the signals controlling the proliferation-differentiation switch in vivo remain elusive. Here, we show that mice carrying a homozygous missense mutation in interferon regulatory factor 6 (Irf6), the homolog of the gene mutated in the human congenital disorders Van der Woude syndrome and popliteal pterygium syndrome, have a hyperproliferative epidermis that fails to undergo terminal differentiation, resulting in soft tissue fusions. We further demonstrate that mice that are compound heterozygotes for mutations in Irf6 and the gene encoding the cell cycle regulator protein stratifin (Sfn; also known as 14-3-3sigma) show similar defects of keratinizing epithelia. Our results indicate that Irf6 is a key determinant of the keratinocyte proliferation-differentiation switch and that Irf6 and Sfn interact genetically in this process.

The university of queensland medical leadership program: a case study.

Changes in modern healthcare's provision, complexity, and workforce demands provide a compelling rationale for an increasing emphasis on leadership development at all levels of training within the medical profession. Undergraduate medical education has traditionally focused on the development of clinical acumen with little emphasis on the development of leadership skills or on the operational and systemic issues surrounding healthcare delivery. Incorporating leadership education and competencies presents a number of challenges to medical schools, including defining the subject area, determining the specific skills and knowledge bases that should constitute the basis of the program, and optimizing training to be integrated into the existing clinical curriculum. We present a case study of the Medical Leadership Program at The University of Queensland School of Medicine that runs concurrent to the undergraduate medical degree. We outline the inception of the program, its aims, participant selection, and program components and reflect on the program to date.

Collagen XXVII organises the pericellular matrix in the growth plate.

In order to characterise the function of the novel fibrillar type XXVII collagen, a series of mice expressing mutant forms of the collagen were investigated. Mice harboring a glycine to cysteine substitution in the collagenous domain were phenotypically normal when heterozygote and displayed a mild disruption of growth plate architecture in the homozygous state. Mice expressing an 87 amino acid deletion in the collagenous domain of collagen XXVII were phenotypically normal as heterozygotes whereas homozygotes exhibited a severe chondrodysplasia and died perinatally from a lung defect. Animals expressing the 87 amino acid deletion targeted specifically to cartilage were viable but severely dwarfed. The pericellular matrix of proliferative chondrocytes was disrupted and the proliferative cells exhibited a decreased tendency to flatten and form vertical columns. Collagen XXVII plays an important structural role in the pericellular extracellular matrix of the growth plate and is required for the organisation of the proliferative zone.