脊椎动物肢的发育和再生.doc

脊椎动物肢的发育和再生 Vertebrate Limb Development and RegenerationHow are these processes involved？这些过程是怎样被涉及到的呢？ 1， Pattern formation directs cell identity and leads to ordered spatial pattern of cell activity模式形成：指导细胞身份并且形成细胞活动的有序的空间结构。2， Positional information directs where organs will form位置信息：指导器官在哪里形成。 3，Induction direction of specific cell fate诱导：特定细胞命运的方向 4，Morphogenesis changing the form of cells形态发生：改变细胞 5，Differentiation acquire functional and structural identity distinct from their surrounding cells分化：获得不同于其周围细胞的结构和功能上的特性The greater the number of divisions, the more distal the cell identity. Apical Ectodermal Ridge (AER)外胚层顶脊1 of 2 organizing regions. 调控区域的其中之一 length of ridge controls width of bud. 嵴的长度控制着芽的宽度 essential for both outgrowth and proximodistal patterning; truncated截短的limbs result after removal. 对于向外生长和靠近远端的模式形成，移除之后导致肢被截短都必不可少。 FGF4: in posterior region - can act as a functional substitute for apical ridge FGF4：在较晚的时期，可以在功能上替代AER. Progress Zone (PZ)渐进带。cells begin to differentiate only after leaving the progress zone.细胞只有在离开渐进带之后才开始分化。ZPA极性活性区diffusible morphogen specifies position of cells along antero-posterior (A/P) axis; by concentration of morphogen, or short-range signals可扩散的形态发生素沿着A/P轴指明细胞位置，通过提高形态发生素的浓度或者缩短信号（传递）的距离 n ZPA and PZ signals are necessary for survival and function of AER; FGFs from AER maintain ZPA and PZ.n positive feedback loop: between SHH protein in mesoderm and FGF4 expression in ridge, via bone morphogenetic proteins (BMPs).What Directs Limb Development?:n The AER is responsible for the proximo下月-distal 末梢patterning of the limb, which occurs over time through the progress zone AER【定外胚层嵴】在渐进带阶段负责肢的下月末梢的形成。 n Signals are sent both from the AER to the progress zone, and from the progress zone to the AER信号既从传递到到渐进带，也从渐进带传送到。n The ZONE OF POLARIZING ACTIVITY (ZPA) is responsible for antero-posterior patterning of the limb【极化活性区】负责肢前后轴的形成。n The ECTODERM controls patterning along the dorso-ventral axis外胚层控制着沿背腹轴的图式形成n Differences in the activation of genes that control the interpretation of positional information is responsible for development of different limb structures (i.e. wing or leg)控制着提供位置信息的不同的基因活动负责不同肢结构的发育。 What Molecules Direct Limb Development？那些分子指导肢的发育？Sonic Hedgehog (Shh) n The Shh gene encodes inductive signaling molecules that function during embryogenesis基因编码诱导在胚胎发生时起作用的信号分子。 n establishing cell fates参与决定细胞命运 Key signal in patterning of the antero-posterior limb axis肢前后轴模式形成的主要信号。n Alx-4 represses Shh expression Alx4抑制Shh 的表达。 Fibroblast Growth Factor 4 (FGF-4) n Member of FGF family FGF家族的成员 Mesodermal cell stimulator and directs developmental signaling胚层细胞刺激物指导发育信号。n FGF-4 -/- die on E 5.0 FGF-4/-死在那啥E 5.0Transcriptionally inactive in adult tissues在成体组织中转录不活跃。 Differential response of Shh expression between chick forelimb and hindlimb buds by FGF-4在FGF-4作用下，Shh在鸡胚前肢和后肢的表达有不同的应答 Apical Ectodermal Ridge AER 顶外胚层嵴。n The AER is needed for Maintaining proliferation of the mesoderm (the AER produces FGF8). The mesenchyme in contact with the AER (progress zone) proliferates instead of differentiating into cartilage and muscle. 维持中胚层的增殖。（顶外胚层嵴产生FGF-8）和AER（渐进带）有关的间质细胞增殖分化为软骨和肌肉。 Maintaining expression of the molecules that generate the anterior-posterior polarity. 维持引起前后轴极性的分子的表达 Interacting with signaling proteins so that each cell receives instructions on how to differentiate.与信号蛋白反应这样每个细胞就能知道如何分化。 Regeneration is the reactivation of development in later life to restore missing tissues 再生是指在后来的生活中为修复失去的组织的一种再激活发育。Mechanisms of Regenerationn Morphallaxis变形再生: - repatterning of existing tissues with very little new growth (E.g. Hydras) 变形再生：已存在的组织和一小部分新生的组织的整合。 n Compensatory Regeneration代偿性再生: - cells divide but maintain their differentiated functions with no formation of dedifferentiated tissues (E.g. Mammalian liver) 代偿性再生：细胞分裂为有其正常分化后的那些功能的组织而不形成去分化组织。 n Epimorphosis新建再生: - adult structures dedifferentiate to form a mass of cells that become respecified重新指定, which is characteristic of regenerating limbs (E.g. Urodele amphibians) 新建再生：成体结构去分化形成被重新指定的具有再分化为肢的特性的大量细胞。 Processes of Limb Regeneration1. Dedifferentiation去分化。 2. Proliferation增殖。3. Differentiation分化。What Happens during Dedifferentiation？n breakdown of extracellular matrices (ECMs) of many cells (fibroblasts, myofibres肌原纤维, etc.) 许多细胞的细胞外基质的破坏。（成纤维细胞，肌原纤维等。） n caused by up-regulation of proteases蛋白酶(acid hydrolases水解酶, matrix metalloproteinases金属蛋白酶) 由蛋白酶调节（水解酶，金属蛋白酶）n cells lose differentiated characteristics细胞失去了已分化的特性。n Become progenitor cells that are able to re-enter the cell cycle and form the regeneration blastema (再生)芽基 恢复成祖细胞再次拥有了从细胞分化周期里再生为芽基的能力。 When Does Proliferation occur?n genes in differentiated tissues are down-regulated基因在已分化的组织中共能下调了 n Gene expression in proliferating mesenchyme of embryonic limb increases在正在增殖的胚胎间充质细胞中基因表达增加。 n cells in regeneration blastema proliferate and redifferentiate to form new structures of the limb再生的肢芽的细胞增殖分化形成肢新的结构。 n Proliferation of Myotubes肌管肌管的增值 n myoblast肌原细胞cells dedifferentiate and join together to produce multinucleated多核的myotube cells肌原细胞再分化参与形成多核肌管细胞 n myotubes brought into the blastema芽基, and forms mononucleated单核的cells that proliferate and differentiate into many tissues肌管细胞进入芽基形成单核细胞最终增殖分化为大量组织。 n myotube nuclei are forced to enter the cell cycle 肌管细胞核被迫进入细胞周期？ What causes cells to re-enter the cell cycle? 什么导致细胞再次进入细胞周期？n suppressor of cell cycle is retinoblastoma protein（成视网膜母细胞瘤蛋白,Rb蛋白一种抑癌蛋白,参与细胞周期调控）成视网膜母细胞瘤蛋白是细胞周期抑制物。 n Serum containin