ERK1/2 signalling dynamics promote neural differentiation by regulating chromatin accessibility and the polycomb repressive complex.

Fibroblast growth factor (FGF) is a neural inducer in many vertebrate embryos, but how it regulates chromatin organization to coordinate the activation of neural genes is unclear. Moreover, for differentiation to progress, FGF signalling must decline. Why these signalling dynamics are required has not been determined. Here, we show that dephosphorylation of the FGF effector kinase ERK1/2 rapidly increases chromatin accessibility at neural genes in mouse embryos, and, using ATAC-seq in human embryonic stem cell derived spinal cord precursors, we demonstrate that this occurs genome-wide across neural genes. Importantly, ERK1/2 inhibition induces precocious neural gene transcription, and this involves dissociation of the polycomb repressive complex from key gene loci. This takes place independently of subsequent loss of the repressive histone mark H3K27me3 and transcriptional onset. Transient ERK1/2 inhibition is sufficient for the dissociation of the repressive complex, and this is not reversed on resumption of ERK1/2 signalling. Moreover, genomic footprinting of sites identified by ATAC-seq together with ChIP-seq for polycomb protein Ring1B revealed that ERK1/2 inhibition promotes the occupancy of neural transcription factors (TFs) at non-polycomb as well as polycomb associated sites. Together, these findings indicate that ERK1/2 signalling decline promotes global changes in chromatin accessibility and TF binding at neural genes by directing polycomb and other regulators and appears to serve as a gating mechanism that provides directionality to the process of differentiation.

A lateral protrusion latticework connects neuroepithelial cells and is regulated during neurogenesis.

Dynamic contacts between cells within the developing neuroepithelium are poorly understood but play important roles in cell and tissue morphology and cell signalling. Here, using live-cell imaging and electron microscopy we reveal multiple protrusive structures in neuroepithelial apical endfeet of the chick embryonic spinal cord, including sub-apical protrusions that extend laterally within the tissue, and observe similar structures in human neuroepithelium. We characterise the dynamics, shape and cytoskeleton of these lateral protrusions and distinguish them from cytonemes, filopodia and tunnelling nanotubes. We demonstrate that lateral protrusions form a latticework of membrane contacts between non-adjacent cells, depend on actin but not microtubule dynamics, and provide a lamellipodial-like platform for further extending fine actin-dependent filipodia. We find that lateral protrusions depend on the actin-binding protein WAVE1 (also known as WASF1): misexpression of mutant WAVE1 attenuated protrusion and generated a round-ended apical endfoot morphology. However, this did not alter apico-basal cell polarity or tissue integrity. During normal neuronal delamination, lateral protrusions were withdrawn, but precocious protrusion loss induced by mutant WAVE1 was insufficient to trigger neurogenesis. This study uncovers a new form of cell-cell contact within the developing neuroepithelium, regulation of which prefigures neuronal delamination. This article has an associated First Person interview with the first author of the paper.

Crumbs2 mediates ventricular layer remodelling to form the spinal cord central canal.

In the spinal cord, the central canal forms through a poorly understood process termed dorsal collapse that involves attrition and remodelling of pseudostratified ventricular layer (VL) cells. Here, we use mouse and chick models to show that dorsal ventricular layer (dVL) cells adjacent to dorsal midline Nestin(+) radial glia (dmNes+RG) down-regulate apical polarity proteins, including Crumbs2 (CRB2) and delaminate in a stepwise manner; live imaging shows that as one cell delaminates, the next cell ratchets up, the dmNes+RG endfoot ratchets down, and the process repeats. We show that dmNes+RG secrete a factor that promotes loss of cell polarity and delamination. This activity is mimicked by a secreted variant of Crumbs2 (CRB2S) which is specifically expressed by dmNes+RG. In cultured MDCK cells, CRB2S associates with apical membranes and decreases cell cohesion. Analysis of Crb2F/F/Nestin-Cre+/- mice, and targeted reduction of Crb2/CRB2S in slice cultures reveal essential roles for transmembrane CRB2 (CRB2TM) and CRB2S on VL cells and dmNes+RG, respectively. We propose a model in which a CRB2S-CRB2TM interaction promotes the progressive attrition of the dVL without loss of overall VL integrity. This novel mechanism may operate more widely to promote orderly progenitor delamination.

Prioritizing a research agenda on built environments and physical activity: a twin panel Delphi consensus process with researchers and knowledge users.

BACKGROUND: The growth of urban dwelling populations globally has led to rapid increases of research and policy initiatives addressing associations between the built environment and physical activity (PA). Given this rapid proliferation, it is important to identify priority areas and research questions for moving the field forward. The objective of this study was to identify and compare research priorities on the built environment and PA among researchers and knowledge users (e.g., policy makers, practitioners). METHODS: Between September 2022 and April 2023, a three-round, modified Delphi survey was conducted among two independent panels of international researchers (n = 38) and knowledge users (n = 23) to identify similarities and differences in perceived research priorities on the built environment and PA and generate twin 'top 10' lists of the most important research needs. RESULTS: From a broad range of self-identified issues, both panels ranked in common the most pressing research priorities including stronger study designs such as natural experiments, research that examines inequalities and inequities, establishing the cost effectiveness of interventions, safety and injuries related to engagement in active transportation (AT), and considerations for climate change and climate adaptation. Additional priorities identified by researchers included: implementation science, research that incorporates Indigenous perspectives, land-use policies, built environments that support active aging, and participatory research. Additional priorities identified by knowledge users included: built environments and PA among people living with disabilities and a need for national data on trip chaining, multi-modal travel, and non-work or school-related AT. CONCLUSIONS: Five common research priorities between the two groups emerged, including (1) to better understand causality, (2) interactions with the natural environment, (3) economic evaluations, (4) social disparities, and (5) preventable AT-related injuries. The findings may help set directions for future research, interdisciplinary and intersectoral collaborations, and funding opportunities.

Parental Perspectives of Sleep in the Home: Shaping Home-School Partnerships in School-Based Sleep Promotion Initiatives.

INTRODUCTION: Sleep is a critical component of child health and the prevention of chronic disease. Children may benefit from school-based sleep promotion; however, parents need to be involved for healthy sleep strategies learned at school to be translated to the home. The objective of this study was to explore parental perspectives on sleep behaviors and responsiveness to school-based sleep promotion. METHODS: Twenty-five parents of school-aged children were purposively sampled for interviews from July 2019 through April 2020 in Alberta, Canada. Descriptive qualitative methodology was used, and data were generated through semistructured interviews and researcher field notes. Interviews were transcribed and themes were identified by using latent content analysis. RESULTS: Three themes emerged from analysis: 1) sleep is valued and supported, 2) barriers to healthy sleep exist, and 3) schools are allies in promoting sleep. Parents perceived that sleep was essential for their child's health, facilitated healthy sleep practices in the home, and highlighted barriers (busy schedules and poor parental role models) that affected sleep. Parents supported and expressed value in school-based sleep promotion and noted factors that affected the success of school-based sleep promotion. CONCLUSION: Parents are responsive to school-based sleep promotion. Promotion efforts should include resources that engage and involve parents in the school community. Throughout the development of resources to support school-based sleep promotion, additional consideration of parent-reported barriers to promoting healthy sleep in the home should be included.

Prioritizing well-being in K-12 education: lessons from a multiple case study of Canadian school districts.

Increasingly, school districts are looking for insights on how to embed a well-being focus across school communities. Well-being in K-12 education is proven to support positive mental health, improve academic performance and contribute to positive outcomes for students and staff. How districts transition to deeply integrate well-being into existing priorities and practices is not well understood. Insights on such shifts can help inform widespread change in education. In 2020, six Canadian school districts participated in case study research to examine how and why districts were able to shift their culture to one that prioritizes well-being. Fifty-five school community members participated in individual semi-structured interviews to explore their perception of well-being in their school communities. Analysis identified six themes: well-being is wholistic and requires balance, student and staff well-being are interconnected, organizational leadership sustains implementation, connection and voice as a catalyst to well-being, building capacity to support well-being action, and charting and re-charting a course. Findings increase our understanding of system-level change, and provide insights to support well-being in education.

Well-being in K-12 education is proven to support positive mental health, improve academic performance and contribute to positive outcomes for students and staff. How school districts can deeply integrate well-being into existing priorities and practices is not well understood. Many districts are looking for insights on how to embed a well-being focus across school communities. These insights can help inform change in K-12 education. In 2020, six Canadian school districts participated in case study research to examine how and why districts were able to shift their culture to one that prioritizes well-being. Fifty-five participants from six districts took part in interviews on the topic of district well-being prioritization. Supporting documents were also reviewed. Qualitative analysis identified six common themes: well-being is wholistic and requires balance, student and staff well-being are interconnected, organizational leadership sustains implementation, connection and voice as a catalyst to well-being, building capacity to support well-being action, and charting and re-charting a course. Study findings increase our understanding of system-level change in K-12 education. Findings provide valuable 'entry points' for school and district leaders to consider when making well-being a priority in their own contexts.

It takes a community: exploring APPLE Schools' impact within and beyond school walls in Canada.

Childhood is a critical stage to develop healthy behaviours, and the school years are an important developmental period in which children are learning and growing. School-based health promotion interventions are increasingly using the comprehensive school health (CSH) approach that has been found effective at improving health behaviours, while adapting to the school and community context to create and sustain a healthy school culture. The interconnected environments of school, home and community are key to the CSH approach, however, there is minimal research that has been conducted to determine the impact at the community-level. This research used a qualitative multiple case study design to explore the influence of a school-based health promotion intervention, APPLE Schools, on the school and community environments from the perspectives of school staff in Alberta, Canada. Twenty-two participants participated in walking interviews in five schools. The walking interview approach combined interviewing and field observation and empowered participants to share their local expertise and knowledge within the context of school and community environments. Interviews were transcribed and analysed using an inductive thematic approach. Four themes were identified: APPLE schools look different, APPLE Schools build champions, APPLE Schools builds community partnerships and APPLE Schools honours community culture. Health promotion practice in schools was uniquely adapted based on strengths and needs of each school and was broadly influenced by the community outside of school walls. In sum, it was found that school-based health promotion reaches beyond school walls and can influence the broader community environment.

Childhood is a critical stage to develop healthy behaviours, and the school years are an important developmental period in which children are learning and growing. School-based health promotion interventions are increasingly using the comprehensive school health (CSH) approach. CSH has been found effective in improving health and educational outcomes, including quality of life, healthy eating, physical activity, mental wellness and academic achievement. The interconnected environments of school, home and community are key to the CSH approach, however, there is minimal research that has been conducted to determine the impact at the community-level. This research used a qualitative multiple case study design to explore the influence of a school-based health promotion intervention, APPLE Schools, on the school and community environments from the perspectives of school staff in Canada. Twenty-two participants from five schools, took part in walking interviews. Interviews were transcribed and analysed for patterns and common themes. Four themes were identified: APPLE schools look different, APPLE Schools build champions, APPLE Schools builds community partnerships and APPLE Schools honours community culture. It was found that school-based health promotion reaches beyond school walls and can influence the broader community environment. This understanding will support stronger school­community relationships in future interventions.

Wnt regulates amino acid transporter Slc7a5 and so constrains the integrated stress response in mouse embryos.

Amino acids are essential for cellular metabolism, and it is important to understand how nutrient supply is coordinated with changing energy requirements during embryogenesis. Here, we show that the amino acid transporter Slc7a5/Lat1 is highly expressed in tissues undergoing morphogenesis and that Slc7a5-null mouse embryos have profound neural and limb bud outgrowth defects. Slc7a5-null neural tissue exhibited aberrant mTORC1 activity and cell proliferation; transcriptomics, protein phosphorylation and apoptosis analyses further indicated induction of the integrated stress response as a potential cause of observed defects. The pattern of stress response gene expression induced in Slc7a5-null embryos was also detected at low level in wild-type embryos and identified stress vulnerability specifically in tissues undergoing morphogenesis. The Slc7a5-null phenotype is reminiscent of Wnt pathway mutants, and we show that Wnt/ß-catenin loss inhibits Slc7a5 expression and induces this stress response. Wnt signalling therefore normally supports the metabolic demands of morphogenesis and constrains cellular stress. Moreover, operation in the embryo of the integrated stress response, which is triggered by pathogen-mediated as well as metabolic stress, may provide a mechanistic explanation for a range of developmental defects.

The essential conditions needed to implement the Indigenous Youth Mentorship Program: a focused ethnography.

BACKGROUND: The Indigenous Youth Mentorship Program (IYMP) is a 20-week communal, relationship-based afterschool healthy living program for Indigenous youth in Canada. IYMP embraces the Anishnaabe/Nehiyawak concepts of Mino-Bimaadiziwin/miyo-pimâtisiwin ("living in a good way") via its core components of physical activities/games, healthy snacks, and relationship-building. A strength of IYMP is that it values autonomy, adaptability, and the school community context. However, this presents challenges when evaluating its implementation, given that traditional implementation science methods tend to oversimplify the process. In response, essential conditions for the implementation of school-based healthy living programs across diverse contexts have been developed. The purpose of this research was to understand the applicability of these essential conditions within the context of IYMP. METHODS: 15 participants (n = 10 Young Adult Health Leaders; n = 5 coordinators) with experience implementing IYMP in the provinces of Alberta, Saskatchewan, Manitoba, and Quebec were purposefully sampled. Focused ethnography was the guiding method and one-on-one semi-structured interviews were used as the data generation strategy. The purpose of the interviews was to understand what conditions are needed to implement IYMP. The interview guide was based on previously established essential conditions developed by the research team. Interviews were audio-recorded and transcribed, and content analysis was used to identify patterns in the data. RESULTS: The overarching theme that emerged from the interviews was the applicability of the essential conditions when implementing IYMP. Participants felt the eight core conditions (students as change agents, school/community-specific autonomy, demonstrated administrative leadership, higher-level support, dedicated champion(s) to engage school community, community support, quality and use of evidence, and professional development) and four contextual conditions (time, funding and project support, readiness and understanding, and prior community connectivity) were necessary, but made suggestions to modify two conditions (youth led and learning opportunities) to better reflect their experiences implementing IYMP. In addition, a new core condition, rooted in relationship, emerged as necessary for implementation. CONCLUSIONS: This research adds to the literature by identifying and describing what is needed in practice to implement a communal, relationship-based afterschool healthy living program. The essential conditions may support other researchers and communities interested in implementing and rippling similar programs.

"We're categorized in these sizes-that's all we are": uncovering the social organization of young women's weight work through media and fashion.

BACKGROUND: For decades, dominant weight discourses have led to physical, mental, and social health consequences for young women in larger bodies. While ample literature has documented why these discourses are problematic, knowledge is lacking regarding how they are socially organized within institutions, like fashion and media, that young women encounter across their lifespan. Such knowledge is critical for those in public health trying to shift societal thinking about body weight. Therefore, we aimed to investigate how young women's weight work is socially organized by discourses enacted in fashion and media, interpreting work generously as any activity requiring thought or intention. METHODS: Using institutional ethnography, we learned from 14 informants, young women aged 15-21, in Edmonton, Canada about the everyday work of growing up in larger bodies. We conducted 14 individual interviews and five repeated group interviews with a subset (n = 5) of our informants. A collaborative investigation of weight-related YouTube videos (n = 45) elicited further conversations with two informant-researchers about the work of navigating media. Data were integrated and analyzed holistically. RESULTS: Noticing the perpetual lack of larger women's bodies in fashion and media, informants learned from an early age that thinness was required for being seen and heard. Informants responded by performing three types of work: hiding their weight, trying to lose weight, and resisting dominant weight discourses. Resistance work was aided by social media, which offered informants a sense of community and opportunities to learn about alternative ways of knowing weight. However, social media alleging body acceptance or positivity content often still focused on weight loss. While informants recognized the potential harm of engagement with commercial weight loss industries like diet and exercise, they felt compelled to do whatever it might take to achieve a "normal woman body". CONCLUSIONS: Despite some positive discursive change regarding body weight acceptance in fashion and media, this progress has had little impact on the weight work socially expected of young women. Findings highlight the need to broaden public health thinking around how weight discourses are (re)produced, calling for intersectoral collaboration to mobilize weight stigma evidence beyond predominantly academic circles into our everyday practices.

Citizen science in monitoring food environments: a qualitative collective case study of stakeholders' experiences during the Local Environment Action on Food project in Alberta, Canada.

BACKGROUND: Citizen science bears potential to build a comprehensive view of global food environments and create a broader discussion about how to improve them. Despite its potential, citizen science has not been fully utilised in food environment research. Thus, we sought to explore stakeholders' experiences of the Local Environment Action on Food (LEAF) project, a community-based intervention that employs a citizen science approach to monitoring food environments. METHODS: We used a qualitative collective case study design to explore citizen science through the LEAF process in seven communities in Alberta, Canada. Data generating strategies included semi-structured interviews with citizen scientists (n = 26), document review of communities' Mini Nutrition Report Cards (n = 7), and researcher observation. Data were analyzed in a multi-phase process, using Charmaz's constant comparison analysis strategy. RESULTS: Analysis revealed two main themes: relationship building and process factors. Communities used three interconnected strategies, engaging the right people, treading lightly, and reaching a consensus, to navigate the vital but challenging relationship building process. Process factors, which were influences on the LEAF process and relationship building, included the local context, flexibility in the LEAF process, and turnover among LEAF community groups. CONCLUSION: Citizen science through the LEAF project supported the creation and application of food environment evidence: it enabled residents to collect and interpret local food environment data, develop realistic recommendations for change, and provided them with an evidence-based advocacy tool to support the implementation of these recommendations. We recommend a web application that enables independent community food environment assessments. Such a tool could stimulate and sustain citizen involvement in food environment efforts, helping to build the necessary evidence base and promote the creation of healthy food environments.

Indigenous Youth Mentorship Program: essential characteristics of a Canadian multi-site community-university partnership with Indigenous communities.

The Indigenous Youth Mentorship Program (IYMP) is a peer-led health promotion program grounded in the teachings of Indigenous scholars. IYMP is delivered as a multi-sited community-university partnership (CUP) with Indigenous communities across Canada for elementary students. A local young adult health leader and high school youth mentors offer students healthy snacks, physical activity games, relationship building activities and traditional cultural teachings. IYMP aims to improve children's health and wellbeing and empower Indigenous youth and communities. The purpose of this descriptive qualitative study was to describe the essential characteristics of this multi-sited CUP as perceived by the IYMP principal investigators (PIs). Key informant interviews were conducted with 5 IYMP PIs (2 Indigenous) and analysed using content analysis. The overarching theme was forming a community of practice (CoP), where people with a common interest share best practices as they interact regularly. Four sub-themes were shared interest for Indigenous health/wellbeing and social justice, relationships, mentorship and taking a decolonizing research approach. The IYMP CoP allowed mentorship to occur across regions. The essential characteristics that made the IYMP CUPs successful could be used to inform other multi-sited CUPs with Indigenous communities. Those with mutual interests in Indigenous health and partnership with Indigenous communities could consider forming a CoP. Within a newly formed CoP, relationships and mentorship can be developed through discussion and activities. It is imperative within the CoP to take a decolonizing approach to research and acknowledge the impact that colonial policies and practices have had on generations of Indigenous peoples.

Local Environment Action on Food project: impact of a community-based food environment intervention in Canada.

Children are exposed to food environments that make nutrient-poor, energy-dense food cheap, readily available and heavily marketed; all conditions with potential negative impacts on diet and health. While the need for programmes and policies that improve the status of food environments is clear, greater public support is needed for governments to act. The purpose of this qualitative collective case study was to examine if community engagement in the Local Environment Action on Food (LEAF) project, a community-based food environment intervention in Alberta, Canada, could build public support and create action to promote healthy food environments. Semi-structured interviews with a purposeful sample of 26 stakeholders from 7 communities explored LEAF's impact and stakeholder experiences creating change. Data collection and analysis were iterative, following Charmaz's constant comparative analysis strategy. Participants reported environmental and community impacts from LEAF. Notably, LEAF created a context-specific tool, a Mini Nutrition Report Card, that communities used to promote and support food environment action. Further, analysis outlined perceived barriers and facilitators to creating community-level food environment action, including level of engagement in LEAF, perceived controllability, community priorities, policy enforcement and resources. Findings from this study suggest that community-based interventions, such as LEAF, can help build community capacity and reduce existing barriers to community-level food environment action. Thus, they can provide an effective method to build public awareness, demand and action for healthier food environments.

An Environmental Scan of Existing Canadian Childcare Resources Targeting Improvements in Health Behaviours.

The objective was to conduct an environmental scan of existing Canadian childcare resources targeting nutrition, physical activity, sedentary behaviour, and/or sleep. A comprehensive search plan was conducted that involved four search strategies: (1) grey literature databases, (2) customized Google search engines, (3) targeted websites, and (4) consultation with content experts. A resource (i.e., information, materials) must have been created by government or an organization/agency within Canada, available in English, intended for childcare educators or directors working with children ≤ 5 years of age, and focused on targeting improvements in nutrition, physical activity, sedentary behaviour, and/or sleep. The quality of each included resource was assessed using a modified version of the Authority, Accuracy, Coverage, Objectivity, Date, Significance checklist. A total of 192 eligible resources were included. Most resources targeted only nutrition (n = 101) or physical activity (n = 60), and few resources targeted only sedentary behaviour (n = 2) or sleep (n = 1). The remaining 28 resources targeted more than one health behaviour. The 4 most common topics of resources were menu/meal planning (n = 55), healthy nutrition practices/environment (n = 37), physical activities/games (n = 33), and nutrition/food literacy (n = 20). Only 52 included resources cited evidence. One-third of the included resources (n = 64) were rated as high quality, including 55 that received a point for the significance criterion. Therefore, numerous high quality Canadian childcare resources exist for nutrition and physical activity. Future resource development is needed for sedentary behaviour and sleep. Findings can assist future intervention work and the database of resources can be utilized by relevant stakeholders to support other childcare initiatives. Supplementary Information: The online version contains supplementary material available at 10.1007/s10643-021-01266-2.

Neural differentiation, selection and transcriptomic profiling of human neuromesodermal progenitor-like cells in vitro.

Robust protocols for directed differentiation of human pluripotent cells are required to determine whether mechanisms operating in model organisms are relevant to our own development. Recent work in vertebrate embryos has identified neuromesodermal progenitors as a bipotent cell population that contributes to paraxial mesoderm and spinal cord. However, precise protocols for in vitro differentiation of human spinal cord progenitors are lacking. Informed by signalling in amniote embryos, we show here that transient dual-SMAD inhibition, together with retinoic acid (dSMADi-RA), provides rapid and reproducible induction of human spinal cord progenitors from neuromesodermal progenitor-like cells. Using CRISPR-Cas9 to engineer human embryonic stem cells with a GFP-reporter for neuromesodermal progenitor-associated gene Nkx1.2 we facilitate selection of this cell population. RNA-sequencing was then used to identify human and conserved neuromesodermal progenitor transcriptional signatures, to validate this differentiation protocol and to reveal new pathways/processes in human neural differentiation. This optimised protocol, novel reporter line and transcriptomic data are useful resources with which to dissect molecular mechanisms regulating human spinal cord generation and allow the scaling-up of distinct cell populations for global analyses, including proteomic, biochemical and chromatin interrogation.

Lineage tracing of axial progenitors using Nkx1-2CreERT2 mice defines their trunk and tail contributions.

The vertebrate body forms by continuous generation of new tissue from progenitors at the posterior end of the embryo. The study of these axial progenitors has proved to be challenging in vivo largely because of the lack of unique molecular markers to identify them. Here, we elucidate the expression pattern of the transcription factor Nkx1-2 in the mouse embryo and show that it identifies axial progenitors throughout body axis elongation, including neuromesodermal progenitors and early neural and mesodermal progenitors. We create a tamoxifen-inducible Nkx1-2CreERT2 transgenic mouse and exploit the conditional nature of this line to uncover the lineage contributions of Nkx1-2-expressing cells at specific stages. We show that early Nkx1-2-expressing epiblast cells contribute to all three germ layers, mostly neuroectoderm and mesoderm, excluding notochord. Our data are consistent with the presence of some self-renewing axial progenitors that continue to generate neural and mesoderm tissues from the tail bud. This study identifies Nkx1-2-expressing cells as the source of most trunk and tail tissues in the mouse and provides a useful tool to genetically label and manipulate axial progenitors in vivo.

Myc activity is required for maintenance of the neuromesodermal progenitor signalling network and for segmentation clock gene oscillations in mouse.

The Myc transcriptional regulators are implicated in a range of cellular functions, including proliferation, cell cycle progression, metabolism and pluripotency maintenance. Here, we investigated the expression, regulation and function of the Myc family during mouse embryonic axis elongation and segmentation. Expression of both cMyc (Myc - Mouse Genome Informatics) and MycN in the domains in which neuromesodermal progenitors (NMPs) and underlying caudal pre-somitic mesoderm (cPSM) cells reside is coincident with WNT and FGF signals, factors known to maintain progenitors in an undifferentiated state. Pharmacological inhibition of Myc activity downregulates expression of WNT/FGF components. In turn, we find that cMyc expression is WNT, FGF and Notch protein regulated, placing it centrally in the signalling circuit that operates in the tail end that both sustains progenitors and drives maturation of the PSM into somites. Interfering with Myc function in the PSM, where it displays oscillatory expression, delays the timing of segmentation clock oscillations and thus of somite formation. In summary, we identify Myc as a component that links NMP maintenance and PSM maturation during the body axis elongation stages of mouse embryogenesis.

Indigenous Youth Mentorship Program: key implementation characteristics of a school peer mentorship program in Canada.

The Indigenous Youth Mentorship Program (IYMP) is a peer-led health promotion program developed for elementary school students in Indigenous school communities in Canada. A local young adult health leader (YAHL) and high school mentors offer students healthy snacks, physical activity games, relationship building activities and cultural teachings. IYMP aims to improve children's health and wellbeing and empower Indigenous youth and communities. The purpose of this focused ethnography was to describe the key characteristics of successful IYMP delivery. Two focus groups were conducted with 16 participants (8 YAHLS and 8 youth mentors) from 7 schools followed by 4 individual interviews (3 YAHLs, 1 youth peer mentor). Transcripts were analyzed using content analysis. Findings were triangulated with IYMP program field observations and notes from IYMP national team meetings. The five characteristics identified as important for IYMP delivery were a sense of ownership by those delivering the program, inclusion of Indigenous Elders/knowledge keepers, establishing trusting relationships, open communication among all stakeholder groups, including community and academic partners, and adequate program supports in the form of program funding, manuals that described program activities, and local and national gatherings between academic and community partners for sharing ideas about the program and its components. This study indicates the importance of respectful partnerships between community and academic leads for program success and sustainability. As IYMP is implemented in more communities and becomes community autonomous, program sustainability may be ensured and implementation challenges mitigated by embedding the identified five essential characteristics within the fabric of IYMP.

Multiple steps characterise ventricular layer attrition to form the ependymal cell lining of the adult mouse spinal cord central canal.

The ventricular layer of the spinal cord is remodelled during embryonic development and ultimately forms the ependymal cell lining of the adult central canal, which retains neural stem cell potential. This anatomical transformation involves the process of dorsal collapse; however, accompanying changes in tissue organisation and cell behaviour as well as the precise origin of cells contributing to the central canal are not well understood. Here, we describe sequential localised cell rearrangements which accompany the gradual attrition of the spinal cord ventricular layer during development. This includes local breakdown of the pseudostratified organisation of the dorsal ventricular layer prefiguring dorsal collapse and evidence for a new phenomenon, ventral dissociation, during which the ventral-most floor plate cells separate from a subset that are retained around the central canal. Using cell proliferation markers and cell-cycle reporter mice, we further show that following dorsal collapse, ventricular layer attrition involves an overall reduction in cell proliferation, characterised by an intriguing increase in the percentage of cells in G1/S. In contrast, programmed cell death does not contribute to ventricular layer remodelling. By analysing transcript and protein expression patterns associated with key signalling pathways, we provide evidence for a gradual decline in ventral sonic hedgehog activity and an accompanying ventral expansion of initial dorsal bone morphogenetic protein signalling, which comes to dominate the forming the central canal lining. This study identifies multiple steps that may contribute to spinal cord ventricular layer attrition and adds to increasing evidence for the heterogeneous origin of the spinal cord ependymal cell population, which includes cells from the floor plate and the roof plate as well as ventral progenitor domains.