脊椎動(dòng)物肢的發(fā)育和再生.doc

脊椎動(dòng)物肢的發(fā)育和再生 Vertebrate Limb Development and RegenerationHow are these processes involved？這些過(guò)程是怎樣被涉及到的呢？ 1， Pattern formation directs cell identity and leads to ordered spatial pattern of cell activity模式形成：指導(dǎo)細(xì)胞身份并且形成細(xì)胞活動(dòng)的有序的空間結(jié)構(gòu)。2， Positional information directs where organs will form位置信息：指導(dǎo)器官在哪里形成。 3，Induction direction of specific cell fate誘導(dǎo)：特定細(xì)胞命運(yùn)的方向 4，Morphogenesis changing the form of cells形態(tài)發(fā)生：改變細(xì)胞 5，Differentiation acquire functional and structural identity distinct from their surrounding cells分化：獲得不同于其周?chē)?xì)胞的結(jié)構(gòu)和功能上的特性The greater the number of divisions, the more distal the cell identity. Apical Ectodermal Ridge (AER)外胚層頂脊1 of 2 organizing regions. 調(diào)控區(qū)域的其中之一 length of ridge controls width of bud. 嵴的長(zhǎng)度控制著芽的寬度 essential for both outgrowth and proximodistal patterning; truncated截短的limbs result after removal. 對(duì)于向外生長(zhǎng)和靠近遠(yuǎn)端的模式形成，移除之后導(dǎo)致肢被截短都必不可少。 FGF4: in posterior region - can act as a functional substitute for apical ridge FGF4：在較晚的時(shí)期，可以在功能上替代AER. Progress Zone (PZ)漸進(jìn)帶。cells begin to differentiate only after leaving the progress zone.細(xì)胞只有在離開(kāi)漸進(jìn)帶之后才開(kāi)始分化。ZPA極性活性區(qū)diffusible morphogen specifies position of cells along antero-posterior (A/P) axis; by concentration of morphogen, or short-range signals可擴(kuò)散的形態(tài)發(fā)生素沿著A/P軸指明細(xì)胞位置，通過(guò)提高形態(tài)發(fā)生素的濃度或者縮短信號(hào)（傳遞）的距離 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【定外胚層嵴】在漸進(jìn)帶階段負(fù)責(zé)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信號(hào)既從傳遞到到漸進(jìn)帶，也從漸進(jìn)帶傳送到。n The ZONE OF POLARIZING ACTIVITY (ZPA) is responsible for antero-posterior patterning of the limb【極化活性區(qū)】負(fù)責(zé)肢前后軸的形成。n The ECTODERM controls patterning along the dorso-ventral axis外胚層控制著沿背腹軸的圖式形成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)控制著提供位置信息的不同的基因活動(dòng)負(fù)責(zé)不同肢結(jié)構(gòu)的發(fā)育。 What Molecules Direct Limb Development？那些分子指導(dǎo)肢的發(fā)育？Sonic Hedgehog (Shh) n The Shh gene encodes inductive signaling molecules that function during embryogenesis基因編碼誘導(dǎo)在胚胎發(fā)生時(shí)起作用的信號(hào)分子。 n establishing cell fates參與決定細(xì)胞命運(yùn) Key signal in patterning of the antero-posterior limb axis肢前后軸模式形成的主要信號(hào)。n Alx-4 represses Shh expression Alx4抑制Shh 的表達(dá)。 Fibroblast Growth Factor 4 (FGF-4) n Member of FGF family FGF家族的成員 Mesodermal cell stimulator and directs developmental signaling胚層細(xì)胞刺激物指導(dǎo)發(fā)育信號(hào)。n FGF-4 -/- die on E 5.0 FGF-4/-死在那啥E 5.0Transcriptionally inactive in adult tissues在成體組織中轉(zhuǎn)錄不活躍。 Differential response of Shh expression between chick forelimb and hindlimb buds by FGF-4在FGF-4作用下，Shh在雞胚前肢和后肢的表達(dá)有不同的應(yīng)答 Apical Ectodermal Ridge AER 頂外胚層嵴。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. 維持中胚層的增殖。（頂外胚層嵴產(chǎn)生FGF-8）和AER（漸進(jìn)帶）有關(guān)的間質(zhì)細(xì)胞增殖分化為軟骨和肌肉。 Maintaining expression of the molecules that generate the anterior-posterior polarity. 維持引起前后軸極性的分子的表達(dá) Interacting with signaling proteins so that each cell receives instructions on how to differentiate.與信號(hào)蛋白反應(yīng)這樣每個(gè)細(xì)胞就能知道如何分化。 Regeneration is the reactivation of development in later life to restore missing tissues 再生是指在后來(lái)的生活中為修復(fù)失去的組織的一種再激活發(fā)育。Mechanisms of Regenerationn Morphallaxis變形再生: - repatterning of existing tissues with very little new growth (E.g. Hydras) 變形再生：已存在的組織和一小部分新生的組織的整合。 n Compensatory Regeneration代償性再生: - cells divide but maintain their differentiated functions with no formation of dedifferentiated tissues (E.g. Mammalian liver) 代償性再生：細(xì)胞分裂為有其正常分化后的那些功能的組織而不形成去分化組織。 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：成體結(jié)構(gòu)去分化形成被重新指定的具有再分化為肢的特性的大量細(xì)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肌原纖維, etc.) 許多細(xì)胞的細(xì)胞外基質(zhì)的破壞。（成纖維細(xì)胞，肌原纖維等。） n caused by up-regulation of proteases蛋白酶(acid hydrolases水解酶, matrix metalloproteinases金屬蛋白酶) 由蛋白酶調(diào)節(jié)（水解酶，金屬蛋白酶）n cells lose differentiated characteristics細(xì)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 恢復(fù)成祖細(xì)胞再次擁有了從細(xì)胞分化周期里再生為芽基的能力。 When Does Proliferation occur?n genes in differentiated tissues are down-regulated基因在已分化的組織中共能下調(diào)了 n Gene expression in proliferating mesenchyme of embryonic limb increases在正在增殖的胚胎間充質(zhì)細(xì)胞中基因表達(dá)增加。 n cells in regeneration blastema proliferate and redifferentiate to form new structures of the limb再生的肢芽的細(xì)胞增殖分化形成肢新的結(jié)構(gòu)。 n Proliferation of Myotubes肌管肌管的增值 n myoblast肌原細(xì)胞cells dedifferentiate and join together to produce multinucleated多核的myotube cells肌原細(xì)胞再分化參與形成多核肌管細(xì)胞 n myotubes brought into the blastema芽基, and forms mononucleated單核的cells that proliferate and differentiate into many tissues肌管細(xì)胞進(jìn)入芽基形成單核細(xì)胞最終增殖分化為大量組織。 n myotube nuclei are forced to enter the cell cycle 肌管細(xì)胞核被迫進(jìn)入細(xì)胞周期？ What causes cells to re-enter the cell cycle? 什么導(dǎo)致細(xì)胞再次進(jìn)入細(xì)胞周期？n suppressor of cell cycle is retinoblastoma protein（成視網(wǎng)膜母細(xì)胞瘤蛋白,Rb蛋白一種抑癌蛋白,參與細(xì)胞周期調(diào)控）成視網(wǎng)膜母細(xì)胞瘤蛋白是細(xì)胞周期抑制物。 n Serum containin