(发育生物学)V-动物身体图式的模式建成(II)课件.ppt

1、(发育生物学）V 动物身体图式的模式建成(II)Patterning the body plan in animals1 Development of the Drosophila body plan1.1 Specification of the antero-posterior and dorso-ventral axis in Drosophila oocyte(体轴建立的设定体轴建立的设定)1.2 Setting up the body axes in Drosophila1.3 Patterning the Drosophila embryo1.4 Establishment of

2、the segment identity along the AP axis in adult Drosophila2 Patterning the vertebrate body plan2.1 Setting up the body axes in amphibians(Xenopus)2.2 Somite formation and antero-posterior patterning(the mesodermal derivative)2.3 Patterning the vertebrate nervous system(the ectodermal derivative)2.4

3、Specifying the left-right axis(left-right asymmetry of internal organs)The body axes are specified during mid-oogenesis through the reciprocal signaling between the oocyte and the surrounding follicle cells The sequential expression of different sets of zygotic genes patterns the body plan along the

4、 AP axisSegment polarity genesHomeotic selector genesAll vertebrates,despite 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)and the post-anal tail The ve

5、rtebral column is divided into cervical(neck),thoracic(chest),lumbar(lower back),and sacral(hip and lower)regionsThe DV axis:the mouth defining the ventral side and the spinal cord the dorsal sideLeft-right symmetry:while the vertebrate body is outwardly symmetric with respect to the left and right

6、sides,single internal organs such as the heart and liver are arranged asymmetrically with respect to the dorsal midlinePatterning the body plan in vertebratesn Early development in Drosophila is largely under the control of maternal factors that sequentially activate a different sets of the embryos

7、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(cell induction).n The experiments of Dr Hans Spemann and his students at

8、the University of Freiburg showed there exists an embryonic organizer(胚胎组织者胚胎组织者)that determines the amphibian axis formation and patterns the embryo along the body axes through inducing such inductive interactions.This organizer is later called Spemann organizer.Patterning the body plan in animals1

9、 Development of the Drosophila body plan1.1 Specification of the antero-posterior and dorso-ventral axis in Drosophila oocyte(体轴建立的设定体轴建立的设定)1.2 Setting up the body axes in Drosophila1.3 Patterning the Drosophila embryo1.4 Establishment of the segment identity along the AP axis in adult Drosophila2

10、Patterning the vertebrate body plan2.1 Setting up the body axes in amphibians(Xenopus)2.2 Antero-posterior patterning and somite formation(the mesodermal derivative)2.3 Patterning the vertebrate nervous system(the ectodermal derivative)2.4 Specifying the left-right axis(left-right asymmetry of inter

11、nal organs)Patterning the body plan in animals1 Development of the Drosophila body plan1.1 Specification of the antero-posterior and dorso-ventral axis in Drosophila oocyte(体轴建立的设定体轴建立的设定)1.2 Setting up the body axes in Drosophila1.3 Patterning the Drosophila embryo1.4 Establishment of the segment i

12、dentity along the AP axis in adult Drosophila2 Patterning the vertebrate body plan2.1 Setting up the body axes in amphibians(Xenopus)2.2 Antero-posterior patterning and somite formation(the mesodermal derivative)2.3 Patterning the vertebrate nervous system(the ectodermal derivative)2.4 Specifying th

13、e left-right axis(left-right asymmetry of internal organs)In the transplantation experiments,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 refere

14、d the dorsal lip cells and their derivatives(chordamesoderm,notochord脊索)as the organizer.The discovery of the Spemann organizer(in 1924)Dr Hans Spemann-the Nobel Laureate in Physiology or Medicine 1935For his discovery of the organizer effect in embryonic developmentThe Spemann organizer in developm

15、ent of the body plan(Mechanisms)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 the organizer to create the antero-posterior and dorso-ventral axes?n How did the patterning of the

16、 embryo along the body axes become accompanied?e.g.How did the different parts of the neural tube become established,with the most anterior becoming the sensory organs and forebrain,and the most posterior becoming spinal cord?n How was the organizer specified and formed?What caused the dorsal blasto

17、pore 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?e.g.How did the different parts of the neural tube become e

18、stablished,with the most anterior becoming the sensory organs and forebrain,and the most posterior becoming spinal cord?The Spemann organizer in development of the body plan(Mechanisms)The developmentally important maternal factors are differentially localized along the animal-vegetal axis in the Xe

19、nopus unfertilized eggsThe Xenopus egg possesses a distinct animal-vegetal axis,with most of the developmentally important maternal products(mRNA/proteins)localized in the vegetal regionVg-1 is a member of TGF-beta family of signaling proteinsThe cortical rotation upon sperm entry can both specify t

20、he dorsal side of the amphibian embryo,and induce formation of the Spemann organizerThe cortical rotation relocates those maternal factors,such as Wnt-11 mRNA and Dishevelled protein originally located at the vegetal pole to a site approximately opposite to the sperm entry.These factors called dorsa

21、lizing factors specify their new location as the future dorsal side of the embryo,thus conferring the dorsal-ventral axisModel of the mechanism by which the Dishevelled protein stabilizes beta-catenin in the dorsal portion of the amphibian eggInduction of the Spemann organizer in the dorsal mesoderm

22、(Molecular pathway)Localization of stablized beta-catenin in the dorsal side of the embryoActivation of Wnt signaling activates genes encoding proteins such as Siamois,a homeodomain transcription factorSiamois and TGF-beta signaling pathway function together to activate the goosecoid gene in the dor

23、sal portionGoosecoid as a transcription factor activates genes whose proteins are responsible for induction of the Spemann organizer in the dorsal mesodermThe role of Wnt pathway proteins in dorsal-ventral axis specification of the Xenopus early embryo E:Activating the Wnt pathway by blocking the en

24、dogenous GSK-3 in the ventral cells of the early embryo leads to formation of a twinned embryo with a second dorsal axisn 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 organiz

25、er to create the antero-posterior and dorso-ventral axes?n How did the patterning of the embryo along the body axes become accompanied?e.g.How did the different parts of the neural tube become established,with the most anterior becoming the sensory organs and forebrain,and the most posterior becomin

26、g spinal cord?The Spemann organizer in development of the body plan(Mechanisms)The functions of the Spemann organizer(I)n The ability to initiate the movements of gastrulation.Once the dorsal portion of the embryo is established,thus specifying the DV axis,the movement of the involuting mesoderm est

27、ablishes the AP axis.In Xenopus(and other vertebrates),the formation of the AP axis follows the formation of the DV axisn The ability to self-differentiate dorsal mesoderm into prechordal plate(脊索前板脊索前板),chordamesoderm(notochord脊索脊索)etcn The ability to dorsalize the ectoderm,inducing the formation o

28、f the neural tube n The ability to dorsalize the surrounding mesoderm into paraxial(somite-forming)mesoderm(When it would otherwise form ventral mesoderm)The functions of the Spemann organizer(II)n The organizer at the beginning of gastrulation functions in setting up the dorsal-ventral axis by secr

29、eting diffusible proteins(Noggin,chordin,and follistatin)that antagonize/block the BMP signal.These diffusible proteins generate a gradient of BMP signaling that specifies the DV axisn The organizer is able to secret the Wnt blockers Cerberus,Dickkopf and Frzb in the anterior portion of the embryo t

30、hat generate a gradient of Wnt signaling.Thus,the Wnt signaling gradient specifies the AP axis.The diffusible signal proteins secreted by the Spemann organizer(I)The Organizer at the beginning of gastrulation functions in setting up the dorsal-ventral axis by secreting diffusible proteins(Noggin,Cho

31、rdin,and Follistatin)that antagonize/block the BMP signal.These diffusible proteins generate a gradient of BMP signaling that specifies the DV axisLocalization of noggin mRNA in the organizer tissuenoggin mRNA accumulates in the dorsal marginal zone at gastrulation(A),or in the dorsal blastopore lip

32、(the Spemann organizer)when cells involute(B)During convergent extension,noggin is expressed in the dorsal mesoderm(the notochord,prechordal plate etc)(the developing Spemann organizer)Noggin protein is important for development of the dorsal and anterior structures of the Xenopus embryoMost top:The

33、 embryo lacks dorsal structures(e.g.neural tube)due to exposure to the UV(blocking the cortical rotation leads to failure of the Spemann organizer formation)The 2nd-4th panel:the rescued embryos with dorsal structures in a dosage-related fasion,when the defect embryo is injected with noggin mRNAThe

34、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.Model for the action of the Organizer in specifying the DV axisP-Smad1 antibody staining shows the gradient of the BMP signaling activity alon

35、g the DV axis in an early gastrulating Xenopus embryoA gradient of BMP4 signaling pattern the mesoderm along the DV axis by eliciting the expression of different genes in a concentration-dependent fashion The trunk mesoderm of a neurula-stage embryo can be subdivided into four regions along the dors

36、o-ventral axis The trunk mesoderm of a neurula-stage embryo can be subdivided into four regions along the dorso-ventral axis The gradient of BMP4 signaling activity patterns the mesoderm along the dorso-ventral axis(subdivision of the mesoderm).High doses of BMP4 activate those genes(e.g,Xvent1)for

37、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 through activating myf5 et al The mesoderm becomes notochord tissue when no BMP4 activity is present in the most dors

38、al regionThe diffusible signal proteins secreted 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.Cerberus,a se

39、creted protein from 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 structuresFrzb,another secreted protein from the organizer is important for development of

40、the most anterior head structuresThe frzb is expressed in the head endomesoderm of the organizer,while chordin is localized in the notochordThe frzb mRNA:dark blueThe chordin mRNA:brownMicroinjection of frzb mRNA into the marginal zone leads to the inhibition of trunk formation(head only),due to ina

41、ctivation of the Wnt signalingThe organizer is able to secret different sets of signal proteins that antagonize/block BMP and(or)Wnt signalingThe Wnt signaling pathway and patterning of the neural tube along the AP axisPatterning the body plan in animals1 Development of the Drosophila body plan1.1 S

42、pecification 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 plan2.1 Specification and setting up of the body axes in amphibians(Xenopus)2.2 Antero-posterior patterning a

43、nd somite formation(the mesodermal derivative)2.3 Patterning the vertebrate nervous system(the ectodermal derivative)2.4 Specifying the left-right axis(left-right asymmetry of internal organs)The antero-posterior axial patterning in vertebratesPatterning of the vertebrate embryo along the AP axis wi

44、ll be focused on:Patterning of the dorsal mesoderm 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.The trunk mesoderm of a neurula-stage embryo can be subdivided into fou

45、r regions along the dorso-ventral axis Neural tube and somites seen by scanning electron microscopyPatterning of the somite-forming mesoderm along the antero-posterior axisn Somites are blocks of mesodermal tissue that are formed after gastrulation.They forms in a well-defined order along the AP axi

46、s 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 skin.n Somites differentiate into particular axial structures depending on their position along the

47、AP axis.The anterior-most somites skullThose posterior to them cervical vertebraeMore posterior ones thoracic vertebrae with ribslumbar vertebrae without ribssacral and caudal vertebrae Specification of the pre-somitic mesoderm by position along the AP axis has occurred before somite formation begin

48、s during gastrulation The positional identity of somites along the AP axis is specified by Hox gene expression(I)n The Hox genes specify the positional identity of somites along the AP axis in the vertebrates n The Hox genes of vertebratesContaining a DNA motif of around 180 base pairs termed the ho

49、meobox(同源同源异型框异型框),which encode a similar DNA-binding region of around 60 amino acids known as the homeodomain.Encoding transcription factorsThe Hox genes were originally identified in Drosophila.Mutations in Hox genes produce a homeotic transformation(同源异型转化同源异型转化)a mutation in which one structure

50、replaces another.For example,the four-winged fly.n Most vertebrates have four separate clusters of Hox genes(Only one cluster of the Hox gene in Drosophila).n A particular feature of the Hox gene expression in both insects and vertebrates is:that genes in each cluster are expressed in a temporal and