Genetics of latent zebrafish melanoblasts

超出所提供的空间。 成熟组织的生长、修复或维持通常需要从干细胞前体募集新细胞。在斑马鱼中，黑色素细胞在胚胎中被切除时从干细胞中重新建立，或者在截肢后再生鳍中。我们的目标是了解在胚胎中建立干细胞的机制的细胞和分子基础，或者干细胞如何调查它们的环境，然后被招募来取代再生组织中缺失的细胞。因此，我们将研究生长因子受体，试剂盒，或其他候选基因和突变的作用，在招募黑素细胞干细胞在幼虫和再生鳍，或不同的信号转导途径如何影响不同的细胞功能的黑素细胞迁移或生存。具体而言，我们将：（1）通过靶向吗啉代失活或致敏试剂盒突变的显性增强子，鉴定特异于黑素细胞迁移或存活的试剂盒依赖性信号转导途径。 (2)确定试剂盒在建立或招募黑素细胞干细胞中的作用，这些干细胞在幼虫黑素细胞激光消融后产生新的黑素细胞，并确定阻止黑素细胞恢复的突变。 (3)再生黑色素母细胞谱系中相对于第一次细胞分裂的Order kit（一种假定的干细胞标记物）和trp2（一种假定的黑色素母细胞标记物）表达。 (4)评估pyewacket突变是否影响第一次再生细胞分裂后干细胞和成黑素细胞命运之间的分配。 这项工作将对理解生长因子受体如何通过多种途径发出信号以影响多种细胞功能以及如何招募潜在干细胞以填补细胞缺陷产生普遍影响。这项工作也将对理解黑素细胞发育的基础生物学产生具体影响，这将为人类色素沉着疾病，黑色素瘤或其他癌症中的生长控制机制提供深入了解。性能现场=

EXCEED THE SPACE PROVIDED. Growth, repair or maintenance of mature tissues often requires recruitment of new cells trom stem cell precursors. In zebrafish, melanocytes are re-established from stem cells when ablated in the embryo, or in regenerating fins following amputation. Our goal is to understand the cellular and molecular basis of mechanisms that establish stem cells in the embryo, or how stem cells survey their environment, and then are recruited to replace missing cells in regenerating tissues. Accordingly, we will study the role of a growth factor receptor, kit, or other candidate genes and mutations, in recruiting melanocyte stem cells in larvae and in regenerating fins, or how different signal transduction pathways affect different cellular functions of melanocyte migration or survival. Specifically, we will: (1) ldentify kit-dependent signal transduction pathways specific to melanocyte migration or survival, by targeted morpholino-inactivation or dominant enhancers of a sensitized kit mutation. (2) Determine the role of kit in establishing or recruiting melanocyte stem cells that make new melanocytes following larval melanocyte laser ablations, and identify mutations that prevent melanocyte recovery. (3) Order kit (a presumptive stem cell marker) and trp2 (a presumptive melanoblast marker) expression with respect to the first cell division in regeneration melanoblast lineage. (4) Assess whether pyewacket mutation affects the allocation between stem cell and melanoblast fates following the first regeneration cell division. This work will have a general impact on understanding how growth factor receptors signal through multiple pathways to affect multiple cellular functions and how latent stem cells are recruited to fill cellular deficits. This work will also have specific impact on understanding the basic biology of melanocyte development, that will provide insight into the growth control mechanisms gone awry in human pigmentation disorders, melanoma or other cancers. PERFORMANCE SITE ========================================Section End===========================================