Slit Fragments Generate Diversity in Axon Guidance Signals

狭缝片段产生轴突引导信号的多样性

• 批准号: 10392317
• 负责人: Thomas Kidd
• 金额: $ 39.58万
• 依托单位: UNIVERSITY OF NEVADA RENO
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-04-15 至 2025-03-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10392317
• 关键词: Address; Adhesions; Affect; Alleles; Antibodies; Axon; Binding Sites; Biological; Biological Assay; Biological Process; Blood Vessels; Brain; Cell Adhesion; Cell Culture Techniques; Cells; Clustered Regularly Interspaced Short Palindromic Repeats; Communicable Diseases; Cues; Data; Development; Down Syndrome Cell Adhesion Molecule; Drosophila genus; Embryo; Experimental Models; Goals; Growth; HIV; In Vitro; Knock-out; Length; Ligands; Malignant Neoplasms; Mediating; Metabolic; Molecular; Molecular Genetics; Mus; Muscle fasciculation; Nerve; Nerve Regeneration; Nervous system structure; Neurons; Outcome; Output; Peptide Hydrolases; Permeability; Phenotype; Physiological; Principal Investigator; Process; Production; Proteins; Proteolytic Processing; Reagent; Recombinant Proteins; Role; Sensory; Signal Transduction; Signaling Molecule; System; Testing; Tissues; Transgenic Organisms; Work; axon growth; axon guidance; base; cell type; design; experimental study; fly; genetic approach; genetic testing; in vivo; in vivo evaluation; inhibitor; mutant; nervous system development; neurodevelopment; novel; programs; receptor; receptor binding; response; tool

Axon guidance is the study of how developing nerves navigate in response to external signals. A remarkably small number of navigational signals have been identified, raising the question of how the complexity of the brain is generated. One solution is that a single ligand can signal in different ways either through the presence of different receptors or through processing that alters receptor binding. Slit is a large secreted protein that typically repels growing axons using Robo receptors. Slit is cleaved into two fragments, Slit-N and Slit-C, which display new biological activities in the nervous system and that in many other tissues. However, the role of the Slit fragments is controversial. The Slit-N fragment contains the Robo binding site and has been shown to be repel axons in in vitro culture systems and so is thought to be the active signaling molecule. Multiple lines of in vivo preliminary evidence in Drosophila suggest that only the full-length (Slit-FL) protein repels axons. This proposal takes an in vivo molecular genetic approach in flies and mice to separate the signaling of Slit-FL from that of the Slit fragments.These two systems will allow us to address the effects of Slit on axon growth, axon branching and regulated adhesion (fasciculation). This work will allow us to determine how a single signal can achieve different biological outcomes. The proposed work has implications for a diverse range of fields, including infectious disease, cancer and nerve regeneration.

轴突引导是研究发育中的神经如何对外部环境做出反应