GENETICS OF LATENT ZEBRAFISH MELANOBLASTS

潜伏斑马鱼黑色素细胞的遗传学

• 批准号: 7867593
• 负责人: STEPHEN L JOHNSON
• 金额: $ 25.34万
• 依托单位: WASHINGTON UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-07-16 至 2011-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7867593
• 关键词: Ablation; Adult; Alleles; Animals; Biological Assay; Bromodeoxyuridine; Chimera organism; Development; Embryo; Engineering; Feedback; Genes; Genetic; Growth; Homeostasis; In Situ; Label; Life Cycle Stages; Medical; Monitor; Mutate; Mutation; Natural regeneration; Pattern; Pigments; Population; Recording of previous events; Recruitment Activity; Regenerative Medicine; Regulation; Role; Signal Transduction; Staging; Stem Cell Development; Stem cells; Temperature; Tissues; Zebrafish; adult stem cell; cell growth; developmental genetics; gene function; genetic analysis; in vivo; insight; melanoblast; melanocyte; mutant; novel; repaired; self-renewal; stem cell population

DESCRIPTION (provided by applicant): Growth, repair and homeostasis of adult tissues suggests that they are monitored and maintained by adult, or quiescent, stem cells. In turn, growth control of the quiescent stem cell requires mechanisms whereby their target tissues keep them in check, allowing stem cell activation when needed. We use developmental and genetic analysis to explore these mechanisms in the zebrafish melanocyte pigment pattern. In this proposal, we take advantage of chemically-induced melanocyte-ablation followed by larval melanocyte regeneration to explore mechanisms of quiescent stem cell growth control. Analyses include (i) BrdU incorporation to study growth histories and relationships of stem cell populations and clonal analysis of GFP expression in mosaic animals, (ii) identification of mutants that are specifically defective for melanocyte regeneration, and identification of the mutated gene, and (iii) whether or how mutant target tissues suppress or keep their sustaining stem cells in check. Thus, this proposal will provide novel insights into the developmental and genetic mechanisms of growth control of quiescent or adult stem cells that will in turn facilitate our ability to harness them for medical applications. Using embryonic or adult stem cells in regenerative medicine to replace damaged or missing tissues requires that we know and can manipulate the signals that act to recruit or drive the stem cells to differentiate, or act to repress their development. We use melanocyte regeneration in zebrafish to identify the developmental and genetic mechanisms that regulate the melanocyte stem cell, towards understanding the general mechanisms that positively and negatively regulate stem cell development in vivo.

描述（由申请人提供）：成人组织的生长、修复和体内平衡表明，它们是由成人或静止的干细胞监测和维持的。反过来，静止干细胞的生长控制需要其靶组织对其进行控制的机制，从而在需要时允许干细胞活化。我们使用发育和遗传分析来探讨这些机制在斑马鱼黑色素细胞色素模式。在这个提议中，我们利用化学诱导的黑素细胞消融，然后通过幼虫黑素细胞再生来探索静止干细胞生长控制的机制。分析包括（i）BrdU掺入以研究干细胞群体的生长历史和关系以及嵌合体动物中GFP表达的克隆分析，（ii）鉴定特异性地缺陷于黑素细胞再生的突变体，以及鉴定突变基因，以及（iii）突变靶组织是否或如何抑制或保持其维持干细胞受到控制。因此，这项建议将提供新的见解的发展和遗传机制的生长控制的静止或成人干细胞，这反过来将促进我们的能力，利用它们的医疗应用。在再生医学中使用胚胎或成体干细胞来替代受损或缺失的组织，需要我们知道并能够操纵用于招募或驱动干细胞分化或抑制其发育的信号。我们利用斑马鱼的黑素细胞再生来确定调节黑素细胞干细胞的发育和遗传机制，以了解体内积极和消极调节干细胞发育的一般机制。