Wnt/Rspondin/ß-catenin signals control axonal sorting and lineage progression in Schwann cell development.

During late Schwann cell development, immature Schwann cells segregate large axons from bundles, a process called "axonal radial sorting." Here we demonstrate that canonical Wnt signals play a critical role in radial sorting and assign a role to Wnt and Rspondin ligands in this process. Mice carrying ß-catenin loss-of-function mutations show a delay in axonal sorting; conversely, gain-of-function mutations result in accelerated sorting. Sorting deficits are accompanied by abnormal process extension, differentiation, and aberrant cell cycle exit of the Schwann cells. Using primary cultured Schwann cells, we analyze the upstream effectors, Wnt and Rspondin ligands that initiate signaling, and downstream genetic programs that mediate the Wnt response. Our analysis contributes to a better understanding of the mechanisms of Schwann cell development and fate decisions.

Understanding disability in healthcare: exploring the perceptions of parents of young people with autism spectrum disorder.

Purpose: How autism spectrum disorder (ASD) is understood (i.e., as a medical problem or natural human variation) has profound implications for how healthcare services are designed and delivered. As the recipients of these services, children and families are highly invested in these debates, yet little research has sought to investigate their views. The purpose of this study was to explore parents' conceptualizations of ASD in relation to disability, and how they align with, or diverge from, conceptualizations they encounter within healthcare.Materials and methods: Nine semi-structured qualitative interviews were conducted with parents of children with ASD and thematically analyzed.Results: The accounts suggested that participants integrated multiple and sometimes contradictory conceptualizations of disability that reflected both "medical" and "social" models and sources of disablement. While the participants often advocated for acceptance and inclusion of their child, the label of "neurodiversity" was commonly rejected due to the concern for potential loss of funding for services.Conclusions: Study findings highlight the relationship between how parents conceptualize ASD and their experiences accessing supportive services within current delivery structures. Implications for ASD service providers emphasize accommodating parents' unique and evolving values and priorities for healthcare and their relation to current service systems.Implications for RehabilitationParents conceptualizations of ASD both inform and are influenced by their experiences of accessing supportive services.This study highlights that parents' perspectives are fluid, context-dependent, and do not exclusively represent a single model or perspective of disability.To meet family needs, service providers including healthcare professionals must recognize parents' unique understandings of their child's ASD and appreciate how healthcare shapes these perceptions.

Gab1 and Mapk Signaling Are Essential in the Hair Cycle and Hair Follicle Stem Cell Quiescence.

Gab1 is a scaffold protein that acts downstream of receptor tyrosine kinases. Here, we produced conditional Gab1 mutant mice (by K14- and Krox20-cre) and show that Gab1 mediates crucial signals in the control of both the hair cycle and the self-renewal of hair follicle stem cells. Remarkably, mutant hair follicles do not enter catagen, the destructive phase of the hair cycle. Instead, hair follicle stem cells lose quiescence and become exhausted, and thus no stem cell niches are established in the bulges. Moreover, conditional sustained activation of Mapk signaling by expression of a gain-of-function Mek1(DD) allele (by Krox20-cre) rescues hair cycle deficits and restores quiescence of the stem cells. Our data thus demonstrate an essential role of Gab1 downstream of receptor tyrosine kinases and upstream of Shp2 and Mapk in the regulation of the hair cycle and the self-renewal of hair follicle stem cells.