7 research outputs found
Analysis of Adhesion Molecules and Basement Membrane Contributions to Synaptic Adhesion at the Drosophila Embryonic NMJ
Synapse formation and maintenance crucially underlie brain function in health and disease. Both processes are believed to depend on cell adhesion molecules (CAMs). Many different classes of CAMs localise to synapses, including cadherins, protocadherins, neuroligins, neurexins, integrins, and immunoglobulin adhesion proteins, and further contributions come from the extracellular matrix and its receptors. Most of these factors have been scrutinised by loss-of-function analyses in animal models. However, which adhesion factors establish the essential physical links across synaptic clefts and allow the assembly of synaptic machineries at the contact site in vivo is still unclear. To investigate these key questions, we have used the neuromuscular junction (NMJ) of Drosophila embryos as a genetically amenable model synapse. Our ultrastructural analyses of NMJs lacking different classes of CAMs revealed that loss of all neurexins, all classical cadherins or all glutamate receptors, as well as combinations between these or with a Laminin deficiency, failed to reveal structural phenotypes. These results are compatible with a view that these CAMs might have no structural role at this model synapse. However, we consider it far more likely that they operate in a redundant or well buffered context. We propose a model based on a multi-adaptor principle to explain this phenomenon. Furthermore, we report a new CAM-independent adhesion mechanism that involves the basement membranes (BM) covering neuromuscular terminals. Thus, motorneuronal terminals show strong partial detachment of the junction when BM-to-cell surface attachment is impaired by removing Laminin A, or when BMs lose their structural integrity upon loss of type IV collagens. We conclude that BMs are essential to tie embryonic motorneuronal terminals to the muscle surface, lending CAM-independent structural support to their adhesion. Therefore, future developmental studies of these synaptic junctions in Drosophila need to consider the important contribution made by BM-dependent mechanisms, in addition to CAM-dependent adhesion
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The World Federation of Neurosurgical Societies Young Neurosurgeons Survey (Part II): Barriers to Professional Development and Service Delivery in Neurosurgery.
BACKGROUND: Strengthening health systems requires attention to workforce, training needs, and barriers to service delivery. The World Federation of Neurosurgical Societies Young Neurosurgeons Committee survey sought to identify challenges for residents, fellows, and consultants within 10 years of training. METHODS: An online survey was distributed to various neurosurgical societies, personal contacts, and social media platforms (April-November 2018). Responses were grouped by World Bank income classification into high-income countries (HICs), upper middle-income countries (UMICs), low-middle-income countries (LMICs), and low-income countries (LICs). Descriptive statistical analysis was performed. RESULTS: In total, 953 individuals completed the survey. For service delivery, the limited number of trained neurosurgeons was seen as a barrier for 12.5%, 29.8%, 69.2%, and 23.9% of respondents from HICs, UMICs, LMICs, and LICs, respectively (P < 0.0001). The most reported personal challenge was the lack of opportunities for research (HICs, 34.6%; UMICs, 57.5%; LMICs, 61.6%; and LICs, 61.5%; P = 0.03). Other differences by income class included limited access to advice from experienced/senior colleagues (P < 0.001), neurosurgical journals (P < 0.0001), and textbooks (P = 0.02). Assessing how the World Federation of Neurosurgical Societies could best help young neurosurgeons, the most frequent requests (n = 953; 1673 requests) were research (n = 384), education (n = 296), and subspecialty/fellowship training (n = 232). Skills courses and access to cadaver dissection laboratories were also heavily requested. CONCLUSIONS: Young neurosurgeons perceived that additional neurosurgeons are needed globally, especially in LICs and LMICs, and primarily requested additional resources for research and subspecialty training
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The World Federation of Neurosurgical Societies Young Neurosurgeons Survey (Part I): Demographics, Resources, and Education.
BACKGROUND: Providing a comprehensive and effective neurosurgical service requires adequate numbers of well-trained, resourced, and motivated neurosurgeons. The survey aims to better understand 1) the demographics of young neurosurgeons worldwide; 2) the challenges in training and resources that they face; 3) perceived barriers; and 4) needs for development. METHODS: This was a cross-sectional study in which a widely disseminated online survey (April 2018-November 2019) was used to procure a nonprobabilistic sample from current neurosurgical trainees and those within 10 years of training. Data were grouped by World Bank income classifications and analyzed using χ2 tests because of its categorical nature. RESULTS: There were 1294 respondents, with 953 completed responses included in the analysis. Of respondents, 45.2% were from high-income countries (HICs), 23.2% from upper-middle-income countries, 26.8% lower-middle-income countries, and 4.1% from low-income countries. Most respondents (79.8%) were male, a figure more pronounced in lower-income groups. Neuro-oncology was the most popular in HICs and spinal surgery in all other groups. Although access to computed tomography scanning was near universal (98.64%), magnetic resonance imaging access decreased to 66.67% in low-income countries, compared with 98.61% in HICs. Similar patterns were noted with access to operating microscopes, image guidance systems, and high-speed drills. Of respondents, 71.4% had dedicated time for neurosurgical education. CONCLUSIONS: These data confirm and quantify disparities in the equipment and training opportunities among young neurosurgeons practicing in different income groups. We hope that this study will act as a guide to further understand these differences and target resources to remedy them