Cell Lineage Analysis in Vertebrate Limb Regeneration

描述（由申请人提供）：再生过程知之甚少。该提案旨在扩大对脊椎动物肢体再生如何发生的科学理解。在有尾目两栖动物中，失去的肢体的再生被认为是通过剩余组织的去分化来产生芽基，然后是细胞增殖和图案化事件，这些事件指导细胞的再分化以产生新肢体的组成部分。在本提案的目标1中，将追踪再生蝾螈肢体内的单个细胞谱系，以确定用于去分化的细胞的来源以及这些细胞在新肢体内的命运。目的2将探讨干细胞对哺乳动物肢体再生的潜在贡献。在哺乳动物中，肢体再生仅限于趾尖，并且随着年龄的增长而变得越来越受到限制。目标2将检验一组特定的干细胞，msxl表达细胞，在指尖发现赋予再生能力的假设。验证这一假设需要将msxl细胞移植到更近的位置，并确定它们是否能在那里诱导再生。如果是的话，这些细胞是否可以被操纵以允许近端元件的再生？

DESCRIPTION (provided by applicant): Regenerative processes are poorly understood. This proposal aims to expand scientific understanding of how regeneration occurs in vertebrate limbs. In urodele amphibians, regeneration of a lost limb is thought to occur by dedifferentiation of remaining tissues to create a blastema, followed by cell proliferation and patterning events that direct the redifferentiation of cells to create components of the new limb. In Aim 1 of this proposal, individual cell lineages within a regenerating axolotl limb will be traced to determine the source of cells used for dedifferentiation and the fate of these cells within the new limb. The potential contribution of stem cells to limb regeneration in mammals will be explored in Aim 2. In mammals, limb regeneration is restricted to digit tips and becomes increasingly restricted distally with age. Aim 2 will test the hypothesis that a specific set of stem cells, msxl-expressing cells, found at the digit tips confers regenerative ability. Testing this hypothesis will involve transplanting msxl cells to more proximal locations and determining if they can induce regeneration there. If so, can the cells be manipulated to allow regeneration of proximal elements?