V动物身体图式的模式建成II学习教案

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1、会计学1V动物身体动物身体(shnt)图式的模式建成图式的模式建成II第一页，共64页。Patterning the body plan in animals1 Development of the Drosophila body plan1.1 Specification of the antero-posterior and dorso-ventral axis in Drosophila oocyte1.2 Setting up the body axes in Drosophila1.3 Patterning the Drosophila embryo2 Patterning the

2、vertebrate body plan2.1 Specification and setting up of the body axes in amphibians (Xenopus)2.2 Somite formation and antero-posterior patterning2.3 Patterning the vertebrate nervous system2.4 Specifying the left-right axis (left-right asymmetry of internal organs)第1页/共63页第二页，共64页。All vertebrates, d

3、espite their many outward differences, have a similar basic body planThe skeleton of a mouse embryo illustrates the vertebrate body plan The AP axis: head, trunk with paired appendages (vertebral column脊柱脊柱(jzh) and the post-anal tailThe vertebral column is divided into cervical (neck), thoracic (ch

4、est), lumbar (lower back), and sacral (hip and lower) regionsThe DV axis: the mouth defining the ventral side and the spinal cord the dorsal side第2页/共63页第三页，共64页。第3页/共63页第四页，共64页。Patterning the body plan in vertebratesn Early development in Drosophila is largely under the control of maternal factors

5、 that sequentially activate a different sets of the embryos own genes (zygotic genes) to pattern the body plan. n Vertebrate axes do not form from localized determinants, as in Drosophila. Rather, they arise progressively through a sequence of inductive interactions between neighboring cells. Amphib

6、ian axis formation is an example of this regulative development. n The experiments of Hans Spemann and his students showed there exists an embryonic organizer, Spemann organizer that determines the amphibian axis formation and patterns the embryo along the body axes through inducing such inductive i

7、nteractions.第4页/共63页第五页，共64页。Patterning the body plan in animals1 Development of the Drosophila body plan1.1 Specification of the antero-posterior and dorso-ventral axis in Drosophila oocyte1.2 Setting up the body axes in Drosophila1.3 Patterning the Drosophila embryo2 Patterning the vertebrate body

8、 plan2.1 Specification and setting up of the body axes in amphibians (Xenopus)2.2 Somite formation and antero-posterior patterning2.3 Patterning the vertebrate nervous system2.4 Specifying the left-right axis (left-right asymmetry of internal organs)第5页/共63页第六页，共64页。In the transplantation experiment

9、s, Hans Spemann and Hilde Mangold showed that the dorsal lip of the blastopore can induce the hosts ventral tissues to form a second embryo with clear antero-posterior and dorso-ventral body axes. Spemann refered the dorsal lip as the organizer.The discovery of the Spemann organizer第6页/共63页第七页，共64页。

10、Dr Hans Spemann-the Nobel Laureate in Physiology or Medicine 1935For his discovery of the organizer effect in embryonic development第7页/共63页第八页，共64页。Mechanisms underlying role of the Spemann organizer in development of the body plann How was the organizer specified and formed? What caused the dorsal

11、blastopore lip to differ from any other region of the embryo?n What factors were being secreted from the organizer to create the antero-posterior and dorso-ventral axes?n How did the patterning of the embryo along the body axes become accompanied?第8页/共63页第九页，共64页。Mechanisms underlying role of the Sp

12、emann organizer in development of the body plann How was the organizer specified and formed? What caused the dorsal blastopore lip to differ from any other region of the embryo?n What factors were being secreted from the organizer to create the antero-posterior and dorso-ventral axes?n How did the p

13、atterning of the embryo along the body axes become accompanied?第9页/共63页第十页，共64页。The developmentally important maternal factors are differentially localized along the animal-vegetal axis in the Xenopus unfertilized eggsThe Xenopus egg possesses a distinct animal-vegetal axis, with most of the develop

14、mentally important maternal products (mRNA/proteins) localized in the vegetal region第10页/共63页第十一页，共64页。Vg-1 is a member of TGF-beta family of signaling proteins第11页/共63页第十二页，共64页。The cortical rotation upon sperm entry can both specify the dorsal side of the amphibian embryo, and induce formation of

15、the Spemann organizerThe cortical rotation relocates those maternal factors , such as Wnt-11 and Dishevelled protein originally located at the vegetal pole to a site approximately opposite to the sperm entry. These factors called dorsalizing factors specify their new location as the future dorsal si

16、de of the embryo, thus conferring the dorsal-ventral axis第12页/共63页第十三页，共64页。第13页/共63页第十四页，共64页。Model of the mechanism by which the Disheveled protein stabilizes beta-catenin in the dorsal portion of the amphibian egg第14页/共63页第十五页，共64页。The role of Wnt pathway proteins in dorsal-ventral axis specifica

17、tion (I)E: Blocking the endogenous GSK-3 in the ventral cells of the early embryo leads to formation of a second set of body axis第15页/共63页第十六页，共64页。The role of Wnt pathway proteins in dorsal-ventral axis specification (II)第16页/共63页第十七页，共64页。Model of the induction of the Spemann organizer in the dors

18、al mesodermLocalization of stablized beta-catenin in the dorsal side of the embryoActivation of Wnt signaling activates genes encoding proteins such as SiamoisSiamois and TGF-beta signaling pathway function together to activate the goosecoid gene in the dorsal portionGoosecoid as a transcription fac

19、tor activates genes whose proteins are responsible for induction of the Spemann organizer in the dorsal mesoderm第17页/共63页第十八页，共64页。n How was the organizer specified and formed? What caused the dorsal blastopore lip to differ from any other region of the embryo?n What factors were being secreted from

20、 the organizer to create the dorso-ventral and antero-posterior axes?n How did the patterning of the embryo along the body axes become accompanied?Mechanisms underlying role of the Spemann organizer in development of the body plan第18页/共63页第十九页，共64页。The functions of the Spemann organizer (I)n The abi

21、lity to self-differentiate dorsal mesoderm into prechordal plate, chordamesoderm (notochord脊索(j su) etcn The ability to dorsalize the surrounding mesoderm into paraxial (somite-forming) mesoderm (When it would otherwise form ventral mesoderm)n The ability to dorsalize the ectoderm, inducing the form

22、ation of the neural tuben The ability to initiate the movements of gastrulation. Once the dorsal portion of the embryo is established, the movement of the involuting mesoderm establishes the AP axis. In Xenopus (and other vertebrates), the formation of the AP axis follows the formation of the DV axi

23、s第19页/共63页第二十页，共64页。The functions of the Spemann organizer (II)n The Organizer functions in setting up the dorsal-ventral axis by secreting diffusible proteins (Noggin, chordin, and follistatin) that antagonize/block the BMP signal. These diffusible proteins generate a gradient of BMP signaling that

24、 specifies the DV axisn The Organizer is able to secret the Wnt blockers Cerberus, Dickkopf and Frzb in the anterior portion of the embryo that generate a gradient of Wnt signaling. Thus, the Wnt signaling gradient specifies the AP axis.第20页/共63页第二十一页，共64页。第21页/共63页第二十二页，共64页。第22页/共63页第二十三页，共64页。第23

25、页/共63页第二十四页，共64页。The diffusible signal proteins secreted by the Spemann organizer (I)The Organizer functions in setting up the dorsal-ventral axis by secreting diffusible proteins (Noggin, Chordin, and Follistatin) that antagonize/block the BMP signal. These diffusible proteins generate a gradient o

26、f BMP signaling that specifies the DV axis第24页/共63页第二十五页，共64页。Localization of noggin mRNA in the organizer tissueAt gastrulation, noggin is expressed in the dorsal blastopore lipDuring convergent extension, noggin is expressed in the dorsal mesoderm (the notochord, prechordal plate etc )第25页/共63页第二十

27、六页，共64页。Noggin protein is important for development of the dorsal and anterior structures of the Xenopus embryoRescue of dorsal structures by Noggin proteinMost top: The embryo lacks dorsal structures due to exposure to the UVThe 2nd-4th panel: the rescued embryos with dorsal structures in a dosage-

28、related fasion, when the defect embryo is injected with noggin mRNAThe bottom: If too much noggin mRNA is injected, the embryo produces dorsal tissues at the expense of ventral and posterior tissue, becoming little more than a head.第26页/共63页第二十七页，共64页。Model for the action of the Organizer in specify

29、ing the DV axisP-Smad1 antibody staining shows the gradient of the BMP signaling along the DV axis in an early gastrulating Xenopus embryoA gradient of BMP4 signaling elicits the expression of different genes in a concentration-dependent fasion 第27页/共63页第二十八页，共64页。The diffusible signal proteins secr

30、eted by the Spemann organizer (II)The Organizer is able to secret the Wnt blockers Cerberus, Dickkopf and Frzb in the anterior portion of the embryo that generate a gradient of Wnt signaling. Thus, the Wnt signaling gradient specifies the AP axis.第28页/共63页第二十九页，共64页。Cerberus, a secreted protein from

31、 the organizer is important for development of the most anterior head structuresInjection of Cerberus mRNA into a vegetal ventral Xenopus blastomere at the 32-cell stage induce ectopic head structures第29页/共63页第三十页，共64页。Frzb, another secreted protein from the organizer is important for development of

32、 the most anterior head structuresThe frzb is expressed in the head endomesoderm of the organizerThe frzb mRNA: dark blueThe chordin mRNA: brownMicroinjection of frzb mRNA into the marginal zone leads to the inhibition of trunk formation, due to inactivation of the Wnt signaling第30页/共63页第三十一页，共64页。T

33、he organizer is able to secret different sets of signal proteins that antagonize/block BMP and (or) Wnt signaling第31页/共63页第三十二页，共64页。第32页/共63页第三十三页，共64页。Mechanisms underlying role of the Spemann organizer in the body axis formationn How was the organizer specified and formed? What caused the dorsal

34、blastopore lip to differ from any other region of the embryo?n What factors were being secreted from the organizer to create the antro-posterior and dorso-ventral axes?n How did the patterning of the embryo along the body axes become accompanied?第33页/共63页第三十四页，共64页。第34页/共63页第三十五页，共64页。The trunk meso

35、derm of a neurula-stage embryo can be subdivided into four regions along the dorso-ventral axis 第35页/共63页第三十六页，共64页。The trunk mesoderm of a neurula-stage embryo can be subdivided into four regions along the dorso-ventral axis Patterning the mesoderm along the dorso-ventral axis (subdivision of the m

36、esoderm) is controlled by the gradient of BMP4 signaling. High doses of BMP4 activate those genes (, Xvent1) for development of the lateral plate mesoderm Intermediate levels of BMP4 instruct formation of the intermediate mesoderm Low doses of BMP4 regulate the paraxial mesoderm differentiation thro

37、ugh activating myf5 et al The mesoderm becomes notochord tissue when no BMP4 activity is present in the most dorsal region第36页/共63页第三十七页，共64页。The antero-posterior axial patterning in vertebratesPatterning of the vertebrate embryo along the AP axis will be focused on:Patterning of the dorsal mesoderm

38、 that forms the somites, the blocks of mesodermal cells that give rise to the skeleton and muscles of the trunkPatterning of the ectoderm that will develop into the nervous system. 第37页/共63页第三十八页，共64页。Patterning the body plan in animals1 Development of the Drosophila body plan1.1 Specification of th

39、e antero-posterior and dorso-ventral axis in Drosophila oocyte1.2 Setting up the body axes in Drosophila1.3 Patterning the Drosophila embryo2 Patterning the vertebrate body plan2.1 Specification and setting up of the body axes in amphibians (Xenopus)2.2 Somite formation and antero-posterior patterni

40、ng2.3 Patterning the vertebrate nervous system2.4 Specifying the left-right axis (left-right asymmetry of internal organs)第38页/共63页第三十九页，共64页。Neural tube and somites seen by scanning electron microscopy第39页/共63页第四十页，共64页。Patterning of the somite-forming mesoderm along the antero-posterior axisn Somi

41、tes are blocks of mesodermal tissue that are formed after gastrulation. They forms sequentially in pairs on either side of the notochord, starting at the anterior end of the embryo or head end. The somites give rise to the vertebrae, to the muscles of the trunk and limbs, and to the dermis of the sk

42、in.n Somites differentiate into particular axial structures depending on their position along the AP axis. The anterior-most somites skullThose posterior to them cervical vertebraeMore posterior ones thoracic vertebrae with ribs第40页/共63页第四十一页，共64页。n The pre-somatic mesoderm is patterned along its AP

43、 axis before somite formation begins during gastrulation.n The positional identity of the somites is specified by the combinatorial expression of genes of the Hox complexs along the AP axis, from the hindbrain to the posterior end, with the order of expression of these genes along the axis correspon

44、ding to their order in the cluster along the chromosomen Mutations or overexpression of a Hox gene results, in general, in localized defects in the region in which the gene is expressed, and cause homeotic transformations（同源(tn yun)异型转化）.Somites are formed in a well-defined order along the antero-po

45、sterior axis第41页/共63页第四十二页，共64页。Specification of the pre-somitic mesoderm by position along the antero-posterior axis has occurred before somite formation begins during gastrulation 第42页/共63页第四十三页，共64页。Identity of somites along the antero-posterior axis is specified by Hox gene expression (I)n The H

46、ox (Homeobox) genes of vertebrates encode a large group of gene regulatory proteins that all contain a similar DNA-binding region of around 60 amino acids known as the homeodomain. The homeodomain is encoded by a DNA motif of around 180 base pairs termed the homeobox, a name that came originally fro

47、m the fact that this gene family was discovered through mutations that produce a homeotic transformationa mutation in which one structure replaces another. For example, the four-winged fly. n Hox genes that specify positional identity along the AP axis were originally identified in Drosophila and it

48、 turned out that related genes are involved in patterning the vertebrate axis 第43页/共63页第四十四页，共64页。Identity of somites along the antero-posterior axis is specified by Hox gene expression (II)n All the Hox genes whose functions are known encode transcriptional factors. Most vertebrates have four separ

49、ate clusters of Hox genes. n A particular feature of the Hox gene expression in both insects and vertebrates is that the genes in each cluster are expressed in a temporal and spatial order that reflects their order on the chromosome. That is-a spatial pattern of genes on a chromosome corresponds to

50、a spatial expression pattern in the embryo (The order of the genes in each cluster from 3，to 5，in the DNA is the order in which they are expressed along the AP axis). n The overall pattern suggests that the combination of Hox genes provides positional identity for each somite. In the cervical region

51、, for example, each somite, and thus each vertebra, could be specified by a unique pattern of Hox gene expression 第44页/共63页第四十五页，共64页。Specification of the identity (characteristic strucutre) of each segment is accomplished by the homeotic selector (同源同源(tn yun)异型选择者异型选择者) geneslab and Dfd-the head s

52、egmentsScr and Antp- the thoracic segmentsUbx - the third thoracic segment AbdA and AbdB-the abdominal segmentsHomeotic gene expression in DrosophilaThere are 2 clusters of the homeotic genes encoding the Antennapedia and bithorax complexes第45页/共63页第四十六页，共64页。Loss-of-function mutations in the Ultrab

53、ithorax gene can transform the 3rd thoracic segment into another 2nd thoracic segment, producing a four-winged fly 第46页/共63页第四十七页，共64页。第47页/共63页第四十八页，共64页。第48页/共63页第四十九页，共64页。Almost every region in the mesoderm along the antero-posterior axis is characterized by a particular set of expressed Hox gen

54、es第49页/共63页第五十页，共64页。第50页/共63页第五十一页，共64页。Patterning the body plan in animals1 Development of the Drosophila body plan1.1 Specification of the antero-posterior and dorso-ventral axis in Drosophila oocyte1.2 Setting up the body axes in Drosophila1.3 Patterning the Drosophila embryo2 Patterning the ver

55、tebrate body plan2.1 Specification and setting up of the body axes in amphibians (Xenopus)2.2 Somite formation and antero-posterior patterning2.3 Patterning the vertebrate nervous system2.4 Specifying the left-right axis (left-right asymmetry of internal organs)第51页/共63页第五十二页，共64页。The ectoderm lying

56、 along the dorsal midline of the embryo becomes specified as neuroectoderm, the neural plate, during gastrulationDuring the stage of neurulation, the neural plate forms the neural tube, which eventually differentiates into the central nervous system第52页/共63页第五十三页，共64页。第53页/共63页第五十四页，共64页。Rhombomere:

57、 菱脑节Branchial arches: 鳃弓第54页/共63页第五十五页，共64页。Patterning the nervous system along the AP axisn Hox genes are expressed in the mouse embryo hindbrain in a well-defined pattern, which closely correlates with the segmental pattern. Thus, Hox gene expression may provide a molecular basis for the identitie

58、s of both rhombomeres (菱脑节) and the neural crest at the different positions in the hindbrain.n Both gene mis-expression or gene knock-outs in mice have alreadly shown that change in the Hox gene expression causes a partial or complete homeotic transformation of one segment into another in the hindbr

59、ain. Thus, the Hox genes determine patterning of the hindbrain region along the AP axis第55页/共63页第五十六页，共64页。第56页/共63页第五十七页，共64页。Patterning the nervous system along the AP axisn Hox genes are involved in patterning the hindbrain, but Hox gene expression can not be detected in the most anterior neural

60、tissues of the mousethe midbrain and forebrain. n Instead, homeodomain transcriptional factors such as Otx and Emc are expressed anterior to the hindbrain and specify pattern in the anterior brain in a manner similar to the Hox gene more posteriorly. In mice, Otx1 and Otx2 are expressed in overlappi

61、ng domains in the developing forebrain and hindbrain, and mutations in Otx1 leads to brain abnormalities and epilepsy第57页/共63页第五十八页，共64页。第58页/共63页第五十九页，共64页。Patterning the body plan in animals1 Development of the Drosophila body plan1.1 Specification of the antero-posterior and dorso-ventral axis in

62、 Drosophila oocyte1.2 Setting up the body axes in Drosophila1.3 Patterning the Drosophila embryo2 Patterning the vertebrate body plan2.1 Specification and setting up of the body axes in amphibians (Xenopus)2.2 Somite formation and antero-posterior patterning2.3 Patterning the vertebrate nervous syst

63、em2.4 The left-right asymmetry of the internal organs第59页/共63页第六十页，共64页。The embryo has a left-right axis in vertebratesn In addition to its dorsal-ventral and anterior-posterior axes, the vertebrate embryo has a left-right axis, that is, there are several internal organs, such as the heart and the g

64、ut tube, that are not evenly balanced on the right and left sides. n In all vertebrates studied so far, the crucial event in left-right axis formation is the expression of a nodal gene in the lateral plate mesoderm on the left side of the embryo. In Xenopus, this gene is Xnr1 (Xenopus nodal-related

65、1). If this gene is ectopically expressed on the right-hand side, the position of the heart (which is normally on the left side) and the coiling of the gut are randomized. 第60页/共63页第六十一页，共64页。The embryo has a left-right axis in vertebratesn What determines the expression of Xnr1 solely on the left-h

66、and side? In Xenopus, the fertilization-induced cytoplasmic rotationThe Vg1 protein, one of TGF-beta family members, expressed throughout the vegetal hemisphere of the Xenopus oocyte, seems to be processed into its active form on the left-hand side of the embryo n The pathway by which the Xnr1 protein instructs formation of the left-right asymmetry is unknown, but one of the key genes activated by Xnr1 appears to be pitx2. 第61页/共63页第六十二页，共64页。pitx2, one of key genes activated by Xnr1, regulates