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Nuclear factor one X (NFIX) is a transcription factor required for normal ependymal development. Constitutive loss of Nfix in mice (Nfix−/−) is associated with hydrocephalus and sloughing of the dorsal ependyma within the lateral ventricles. Previous studies have implicated NFIX in the transcriptional regulation of genes encoding for factors essential to ependymal development. However, the cellular and molecular mechanisms underpinning hydrocephalus in Nfix−/− mice are unknown. To investigate the role of NFIX in hydrocephalus, we examined ependymal cells in brains from postnatal Nfix−/− and control (Nfix+/+) mice using a combination of confocal and electron microscopy. This revealed that the ependymal cells in Nfix−/− mice exhibited abnormal cilia structure and disrupted localisation of adhesion proteins. Furthermore, we modelled ependymal cell adhesion using epithelial cell culture and revealed changes in extracellular matrix and adherens junction gene expression following knockdown of NFIX. Finally, the ablation of Nfix from ependymal cells in the adult brain using a conditional approach culminated in enlarged ventricles, sloughing of ependymal cells from the lateral ventricles and abnormal localisation of adhesion proteins, which are phenotypes observed during development. Collectively, these data demonstrate a pivotal role for NFIX in the regulation of cell adhesion within ependymal cells of the lateral ventricles. [ABSTRACT FROM AUTHOR]

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Starting in 1991, the Medical College of Wisconsin's (MCW) primary care-focused faculty development programs have continuously evolved in order to sustain tight alignment among faculty members' needs, institutional priorities, and academic reward structures. Informed by literature on the essential competencies associated with academic success and using educational methods demonstrated to achieve targeted objectives, MCW's initial 1.5-day per month comprehensive faculty development programs prepared faculty as clinician-researchers, leaders, and educators. As institutional priorities and faculty roles shifted, a half-day per month advanced education program was added, and the comprehensive faculty development program transitioned to its current half-day per month program. Using a modular approach, this program focuses exclusively on clinician-educator competencies in curriculum, teaching, leadership, evaluation, and learner assessment. Instructional methods combine interactive, face-to-face sessions modeling a range of instructional strategies with between-session assignments now supported through an e-learning platform. All participants complete a required project, which addresses a divisional or departmental need, meets standards associated with scholarship, and is submitted to a peer-reviewed forum. To date, over 115 faculty members have enrolled in MCW's faculty development programs. Program evaluation over the 15-year span has served to guide program revision and to provide clear evidence of program impact. A longitudinal evaluation of comprehensive program graduates from 1993 to 1999 showed that 88% of graduates' educational projects were implemented and sustained more than one year after program completion. Since 2001, each participant, on average, attributes more than two peer-reviewed presentations and one peer-reviewed publication to program participation. Based on 15 years of evaluation data, five tenets associated with program success are outlined.