发育对进化的限制PPT课件

1、发育对进化的限制发育对进化的限制22章 第六节 李江湲 刘子熠 戈奕文 孟亚平2013.6.13 现有生物大致可分为35个门类，形态模式各不相同。除现有生物门类形态模式外还可以想象出很多另外的形态模式，比如科幻小说笔下的那些动物形态。但是现实生活中，我们从没见过长翅膀的猪。表型发育对进化形成的限制 发育限制（developmental constraints）目目 录录形态限制 morphological constraint1 物理限制 physica constraint23 系统发生限制 phyletic constraint 现在动物只有大约35种形态模式。这是因为动物形态发生受到进化

2、选择的压力，限制了它的发育命运。 发育制约进化的因素至少有3种：1一、一、 物理限制物理限制 physica constraint1、扩散、渗透压、物理支撑使形态发生具有固定的趋势 例如：血液不可能在一个旋转的器官循环带有旋转附肢的脊椎动物不可能出现。2、构造力学和流体力学使世界上不可能形成5尺高的巨型蚊子或者25尺长的大牙。13、组织的可塑性和拉伸强度 例如：二裂果蝇的精子有58mm长的鞭毛，睾丸完全发育要17天。多种假说可以解释巨型精子的进化这种精子为受精卵的发育提供营养，作为直接的亲代投资；它们大到可以封锁雌性的生殖道，防止精子竞争；它们每一个都大到能被传递给雌性，因而雄性只需要生产数量

3、足够使可用的卵子受精的精子。因为这种精子如此巨大，受精的成功率增加了(Mry & Joly 2002)。为了形成这些异常长的鞭毛，构成染色体轴丝的微管蛋白就要受到某种物理属性的限制。形态发生的6种细胞行为（细胞分裂、生长、形态变化、迁移、死亡、基质分泌）都受到物理因素的制约 例例1 1例一：细胞形态的稳定性是由细胞-基底系统的最小自由能来调控的。The Effects of Substrate / Cell System Rigidity on Hepatic and Hepatocellular Carcinoma Cell Migration 重庆大学博士学位论文例二：机械拉伸可通

4、过骨架的重排调整细胞形态 例例2 2血液循环系统组织工程流变学基础研究 生物医学工程学杂志2004 对-actin 的免疫组织化学染色结果表明：应变 10%，0.67Hz的周期拉伸 6 小时后，血管平滑肌细胞内的-actin 含量上升，且呈束状沿细胞长轴排列，随时间的延长，束状结构（应力纤维）逐渐增粗。图 3.7 最大应变 10%的周期拉伸作用下血管平滑肌细胞的取向调整(10)a) 对照组b) 拉伸 3 小时c) 拉伸 6 小时d) 拉伸 12 小时不同基底拉伸过程对细胞生长、取向影响及其骨架重排机制探讨 重庆大学博士学位论文 例例2 2 例例3 3殖，但是正常细胞长到融合状态后，细胞相互接触

5、后细胞的分裂行为就停止了，而肿瘤细胞的生长则丢失了这种“接触抑制”行为。材料的力学特性是如何变细胞生长状态，破坏组织结构和诱导肿瘤形成的内在机制需要了解基底力学特性对相关信号通路的影响。例三、基底/细胞系统刚度对肝细胞和肝癌细胞迁移的调节作用 在肿瘤生长环境中的非细胞因素如改变细胞外基底的硬度也直接或间接的影响肿瘤进程。 一个关于基底刚度诱导肿瘤发生的经典实验发现，将一小块硬金属或是塑料植入动物体内时会诱导癌症的形成。同样的材料，如果是以粉末的形式植入体内的就不会形成肿瘤。我们知道正常细胞和肿瘤细胞都可以在硬基底上增无论在软基底还是在硬基底上，L02（正常肝细胞） 的杨氏模量都高于 M3 （肝

6、癌细胞）。 这些结果提示 M3 细胞柔韧度增加，这一方面将提高它们的形变能力以利于肿瘤细胞的跨膜侵袭；另一方面， 还可能影响与迁移相关的蛋白表达。The Effects of Substrate / Cell System Rigidity on Hepatic and Hepatocellular Carcinoma Cell Migration 重庆大学博士学位论文 硬胶原基底不利于细胞的侵袭，而软胶原基底则促进 L02 和 M3 细胞的侵袭。但是无论在硬基底上还是软基底上，M3 细胞的侵袭率都显著高于 L02 细胞。 胚胎发育如果偏离正常发育途径，那么它们偏离的方式是有限的。脊椎动物附肢

7、的形成，为形态限制提供了范例。 在过去漫长的3亿年中，脊椎动物附肢发生存在许多变异，但是有些变异从未发生过，比如：中指比两边侧指短。这说明脊椎动物的附肢发育遵守一定的法则并受其限制。限制附肢发育的法则之一可能是“反应扩散模型”。二、形态限制二、形态限制 反应-扩散模型由计算机科学创始人之一的Allen Turing于1952年提出，在他的模型中，两种均匀分散的物质P、S相互作用，物质P能够诱导产生更多物质P和物质S的产生，而物质S则能抑制物质P的产生。 反应扩散模型预测某物质的高浓度和低浓度会存在交叉现象，当物质浓度高于一定的阈值时，细胞便会接受指令沿某一特定方向分化。Turing 模型已经在

8、复制的极性结构以及哺乳动物和与的色素模型中得到验证。内容页内容页Reaction-Diffusion Model as a Framework for Understanding Biological Pattern FormationThe reaction-diffusion (RD) model proposed by Alan Turing is a masterpiece of this sort of mathematical modeling, one that can explain how spatial patterns develop autonomously.“the

9、mutual interaction of elements results in spontaneous pattern formation. ” The RD model is now recognized as a standard among mathematical theories that dealwith biological pattern formation.内容页内容页 The elements selected by Turing were a theoretical pair of interacting molecules diffused in a continu

10、ous field. In his mathematical analysis, Turing revealed that such a system yields six potential steady states, depending on the dynamics of reaction term and wavelength of the pattern and Supporting Online Material (SOM) 内容页内容页Such phase unification is seen in such systems as circadian rhythms and

11、the contraction of heart muscle cellsthe system forms salt-and-pepper patterns, such as are made when differentiated cells inhibit the differentiation of neighboring cellsa traveling wave is generated. Biological traveling waves caused by this mechanism include the spiral patterns formed by the soci

12、al amoeba Dictyostelium discoideumon aggregation , and the wave of calcium ions that traverses the egg of the frog Xenopus laevis on sperm entry.内容页内容页The intricate involutions of seashells, the exquisite patterning of feathers, and the breathtakingly diverse variety of vertebrate skin patterns have

13、 all been modeled within the framework of the Turing model内容页内容页例1、Turing Patterns in Vertebrate SkinFig. 3. Movement of zebrafish stripes and the interaction network among thepigment cells. T he pigment pattern of zebrafish is composed of b lack pigment cells (melanophores) and yellow pigment cells

14、 (xanthophores) . The pattern is made by the mutual interaction between these cells. (A) Melanophores in the two black stripes were ablated by laser, and the process of recovery was recorded. (B) Results of simulationby the Turing model. Following laser ablation of pigment cells in a pair of black h

15、orizontal stripes, the lower line shifts upward before stabilizing in a Bell -like curve (Fig. 3A) As a result, the spatial interval between the lines is maintained , even when their direction changes. This striking behavior is predicted bysimulation (Fig. 3B).内容页内容页Work to date has shown that the s

16、kin patterns of this fish are set up and maintained by interactions between pigmented cells . Nakamasu worked out the interaction network among the pigment cells. Although the shape of the network is different from t hat of t he original Turing model, it fits the short -range positive , long-range n

17、egative feedback description (The mutual inhibition between black and yellow cells behaves as a positive feedback loop, as the expansion of black cells weakens their counterpart.)添加标题添加标题例2、Other well-studied examples include the regular disposition of feather buds in chick and of hair follicles in

18、mice . Jung et al .showed that the spatially periodic pattern of feather buds regenerates even when the skin is recombined from dissociated cells . In the case of mouse hair follicles, alteration of the amount of putative key factors changes the pattern in a manner predicted by computer simulation.

19、Sick et al .used overexpression and inhibition of Wnt and Dkk in fetal mouse to study how such perturbations might affect the patterning of follicle formationThey suggested that Wnt serves as a short-range activator, and Dkk as a long-range inhibitor, in this system添加标题添加标题例3、Establishment of right-

20、left a symmetry in vertebrates Establishment of right-left a symmetry in vertebrates is triggered bythe unidirectional rotation of cilia at the node, followed by the interaction of Nodal and Lefty that amplify and stabilize faint differences in gene expression . Nodal enhances both its own expressio

21、n and that of Lefty, and Lefty inhibits the activity of Nodal. The fact that Lefty spreads further than Nodal suggests that the inhibitory interaction propagates more quickly than does its activating counterpart, which as we have seen, indicates that this system fulfills the fundamental requirements

22、 for Turing pattern formation添加标题添加标题例4、In vertebrate limb development, precartilage condensation, which i slater replaced by skeletal bone, occurs periodically along the anterior-posterior axis of the distal tip region.TGF- b can stimulate its own production and trigger precartilage condensation, a

23、nd t he sites of incipient condensation exert a laterally acting inhibitory effect on chondrogenesis. Although no candidate inhibitor has been identified, an interaction net-work comprising TGF-b function and precartilage condensation may satisfy the short-range activatio n and long-range inhibition

24、 criteria .Miura and Shiota have shown that nearly periodic spatial patterns of chondrogenesis occur in the culture of dissociated limb cells in vitro, and that the addition of TGF- b changes the pattern in a manner consistent with the predictions of Turing s model Turing model has long bee n sugges

25、ted to describe the underlying mechanism. In this system, transforming growth factorb (TGF-b) has been invoked as a candidate for the activator molecule .例5、Reactiondiffusion models of within-feather pigmentation patterningExamples of the diversity of within-feather pigmentation patterns：添加标题添加标题The

26、 activating signal reinforces its own production and the production of the inhibitory signal, which inhibits the production of the activating signal. Both activating and inhibitory signals diffuse and decay over time.添加标题添加标题Real and simulated pigment pattern transitions by Reactiondiffusion models

27、among feathers from the same tract:(a) transition from bars to chevrons ( Eupodotis atra etoschae, Otidae, KU 86156); ( b) simulated transition from bars to chevrons; ( b) simulated transition from bars to chevrons; ( c) transition from bars to distal pair of lateral dots ( Pytilia melba, Estrildida

28、e, KU REM 795); (d ) transition from bars to a series of laterally paired dots ( Spilornis cheela panayensis, KU 43654); ( e) simulated transition from bars to distal pair of dots to a series of laterally paired dots;( f ) transition from bars to an array of dots ( Numida meleagris reichenowi, Numid

29、idae, KU 29479); ( g) simulated transition from bars to an array of dots.系统发生限制系统发生限制phylogeny restriction1.系统发生决定遗传物质，进而决定了发育基本框架系统发生决定遗传物质，进而决定了发育基本框架进化中每个门进化中每个门类的动物都有类的动物都有其独特的结构，其独特的结构，该结构一旦经该结构一旦经诱导作用形成诱导作用形成后，在其进化后，在其进化过程中，就很过程中，就很难重新启动新难重新启动新的发育机制。的发育机制。脊索结构和功能的保守性 脊索是脊索动物有别于其它动物的重要特征。 脊索最初是

30、起支持体轴作用。比如文昌鱼中脊索终身保留。而在进化过程中，脊椎逐渐代替脊索。我的脊索起支持体轴作用脊椎代替脊索起支持作用 虽然脊椎动物成体中没有脊索的结构，但是脊索在脊椎动物胚胎发育过程中并没有消失，在胚胎中仍起支持作用，同时还能促进神经管和生骨节的分化。 脊索由脊椎代替，不是因为脊索没有用了，而是脊索的功能不够用了，所以在脊索的基础上进一步进化成脊椎，而不是把脊索废弃掉，重新启动脊椎的发育机制。 中生代的哺乳动物古兽目在灭绝之前分化出了有袋类和有胎盘类两大哺乳动物新类群。这两大类哺乳动物拥有更加完善的适应变化着的生态环境的能力，它们顽强地度过了中生代之末的大劫难，并在随后的新生代里占据了恐龙

31、空出来的几乎所有生态位，分布遍及了地球上几乎每一个角落。古兽目有袋类有胎盘类可见，有袋类和有胎盘类动物有同等的进化地位。附肢的进化：附肢的进化：但是有胎盘类动物附肢变化多样，如爪、翼。鳍状肢、手等为什么我们的为什么我们的“胳膊胳膊”都长一都长一样？样？小鼠的爪 蓝鲸的鳍 海狮的鳍状肢 人手 蝙蝠的翼 负鼠的爪 有袋类的附肢却基本相同 Sears认为有袋类胎儿必须爬到母亲育儿袋内，这一需求限制了其附肢的发育，因为要爬到育儿袋内，所以附肢肌肉和软骨需要很早发育成形，以便完成紧抓和爬行动作。因此，有袋类附肢性状发育的其它可能变异都被有效排除了，不会像胎盘类一样发展出具有其他功能的鳍或是翅膀。 有袋类

32、的系统发生（进化历史）限制了其前肢的进化。2.基因的多效性（pleiotropy）限制进化速度 基因的多效性是指一个基因在不同细胞中行使不同功能的现象。 分节基因调控网络在所有昆虫中相当保守，是因为这些基因在几条不同途径中行使功能，这使得发育途径难以变化，限制了替代机制出现的可能性。Conservation of the segmented germband stage: robustness or pleiotropy?分节极性基因网络组成cicubitus interruptus (CI)enengrailed (EN)hhhedgehog (HH)ptcpatched (PTC)wgwi

33、ngless (WG)PHpatchedhedgehog complexCNrepressor fragment of ciTable1. Constituents of the segment polarity gene network modeled by von Dassow et al. 14Conservation of the segmented germband stage: robustness or pleiotropy?几种保守的i信号通路的分子 Fig. 4. Hypomorphic Wg-1 mutant showing a failure in the develop

34、ment of antennae, wings, halteres and thorax (half of the thorax is missing, scutellum missing and hairs deranged (reproduced, with permission, from Ref. 28).例如Wg-1的突变涉及各个方面的表型，表现为触角、翅、平衡棒、胸部发育缺陷Conservation of the segmented germband stage: robustness or pleiotropy?基因多效性可能是构成哺乳类所见到的发育限制的基础 为什么鸟类有10多

35、个颈椎（cervical vertebrae）而哺乳类只有7个颈椎？哺乳类多一个或少一个颈椎会出现什么现象？Why Do Almost All Mammals Have Seven Cervical Vertebrae? Developmental Constraints, Hox Genes, and Cancer FRIETSON GALIS*TABLE 1. The incidence of a cervical rib in children with embryonal cancers1Type of childhood cancer Number of cases Incidenc

36、e of a cervical ribNeuroblastoma 88 33%Brain tumour 234 27.4%Leukemia 227 26.8%Soft tissue sarcoma 98 24.5%Wilms tumour 68 23.5%Ewing sarcoma 35 17.1%1Data from Schumacher et al. (.92).Why Do Almost All Mammals Have Seven Cervical Vertebrae? Developmental Constraints, Hox Genes, and Cancer FRIETSON

37、GALIS*78%的人类胚胎具有多一个前端颈椎的会的人类胚胎具有多一个前端颈椎的会在出生前死亡，侥幸能出生的其中在出生前死亡，侥幸能出生的其中83%在在1年内死亡。年内死亡。Gails认为Changes in Hox gene expression, which lead to changes in the number of cervical vertebrae, are associated with neural problems and with an increased susceptibility to early childhood cancer and stillbirths（

38、死产）. 在脊椎动物中，Hox基因表达与骨骼轴性、神经系统发育有关。而在人和小鼠中，已发现Hox基因与细胞的正常和不正常增殖有关。In vertebrates, Hox genes are involved in the development of the skeletal axis and the nervous system, among other things. In humans and mice, Hox genes have been shown also to be involved in the normal and abnormal (cancer) proliferat

39、ion of cell lines; several types of cancer in young children are associated with abnormalities in Hox gene expression and congenital anomalies.Why Do Almost All Mammals Have Seven Cervical Vertebrae? Developmental Constraints, Hox Genes, and Cancer FRIETSON GALIS*3. 沙漏模型对进化的限制embryogenesis diverges

40、more extensively in the early and late stages than the middle stage。该该middle stage即即种系特征性发育阶段种系特征性发育阶段(phylotypic stage)：Baers laws (embryology)1.General characteristics of the group to which an embryo belongs develop before special characteristics.2.General structural relations are likewise formed

41、before the most specific appear.3.The form of any given embryo does not converge upon other definite forms but, on the contrary, separates itself from them.4.Fundamentally, the embryo of a higher animal form never resembles the adult of another animal form, such as one less evolved, but only its embryo.Figure 1 | The developmental hourglass, as revealed by comparative genomics. Mid-embryogenesis is marked by the phylotypic stage, a period of minimal anatomical divergence betwe