V動物身體圖式的模式建成IIPPT學習教案

1、會計學1V動物身體圖式的模式建成動物身體圖式的模式建成IIPatterning 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

2、 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頁/共63頁All vertebrates, despite their many outwar

3、d 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 tailThe vertebral column is divided into cervical (neck), thoracic (chest), lumbar (lower back), and

4、 sacral (hip and lower) regionsThe DV axis: the mouth defining the ventral side and the spinal cord the dorsal side第2頁/共63頁第3頁/共63頁Patterning the body plan in vertebratesn Early development in Drosophila is largely under the control of maternal factors that sequentially activate a different sets of

5、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. Amphibian axis formation is an example of this regulat

6、ive 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 interactions.第4頁/共63頁Patterning the body plan in

7、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 plan2.1 Specification and setting up of the body axes in

8、 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頁/共63頁In the transplantation experiments, Hans Spemann and Hilde Mangold showed that the dorsal lip of th

9、e 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頁/共63頁Dr Hans Spemann-the Nobel Laureate in Physiology or Medicine 1935For his di

10、scovery of the organizer effect in embryonic development第7頁/共63頁Mechanisms underlying role of the Spemann 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 bei

11、ng 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頁/共63頁Mechanisms underlying role of the Spemann organizer in development of the body plann How was the organizer specified and formed?

12、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 embryo along the body axes become accompanied?第9頁/共63頁The developmentally im

13、portant 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 developmentally important maternal products (mRNA/proteins) localized in the vegetal region第10頁/共63頁Vg-1 is a

14、 member of TGF-beta family of signaling proteins第11頁/共63頁The cortical rotation upon sperm entry can both specify the dorsal side of the amphibian embryo, and induce formation of the Spemann organizerThe cortical rotation relocates those maternal factors , such as Wnt-11 and Dishevelled protein origi

15、nally 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 side of the embryo, thus conferring the dorsal-ventral axis第12頁/共63頁第13頁/共63頁Model of the mechanism by which the Disheveled

16、protein stabilizes beta-catenin in the dorsal portion of the amphibian egg第14頁/共63頁The role of Wnt pathway proteins in dorsal-ventral axis specification (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頁/共63頁The role of Wn

17、t pathway proteins in dorsal-ventral axis specification (II)第16頁/共63頁Model of the induction of the Spemann organizer in the dorsal mesodermLocalization of stablized beta-catenin in the dorsal side of the embryoActivation of Wnt signaling activates genes encoding proteins such as SiamoisSiamois and T

18、GF-beta signaling pathway function together to activate the goosecoid gene in the dorsal portionGoosecoid as a transcription factor activates genes whose proteins are responsible for induction of the Spemann organizer in the dorsal mesoderm第17頁/共63頁n How was the organizer specified and formed? What

19、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 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 S

20、pemann organizer in development of the body plan第18頁/共63頁The functions of the Spemann organizer (I)n The ability to self-differentiate dorsal mesoderm into prechordal plate, chordamesoderm (notochord脊索) etcn The ability to dorsalize the surrounding mesoderm into paraxial (somite-forming) mesoderm (W

21、hen it would otherwise form ventral mesoderm)n The ability to dorsalize the ectoderm, inducing the formation 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 axi

22、s. In Xenopus (and other vertebrates), the formation of the AP axis follows the formation of the DV axis第19頁/共63頁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 antagon

23、ize/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 that generate a gradient of Wnt signaling. Thus, the Wnt signaling g

24、radient specifies the AP axis.第20頁/共63頁第21頁/共63頁第22頁/共63頁第23頁/共63頁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

25、. These diffusible proteins generate a gradient of BMP signaling that specifies the DV axis第24頁/共63頁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 notocho

26、rd, prechordal plate etc )第25頁/共63頁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 dor

27、sal structures in a dosage-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頁/共63頁Model for the action of the Orga

28、nizer in specifying 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頁/共63頁The diffusible signal proteins

29、 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.第28頁/共63頁Cerberus, a secreted protein from the o

30、rganizer 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頁/共63頁Frzb, another secreted protein from the organizer is important for development of the most anteri

31、or 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頁/共63頁The organizer is able to sec

32、ret different sets of signal proteins that antagonize/block BMP and (or) Wnt signaling第31頁/共63頁第32頁/共63頁Mechanisms underlying role of the Spemann organizer in the body axis formationn How was the organizer specified and formed? What caused the dorsal blastopore lip to differ from any other region of

33、 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頁/共63頁第34頁/共63頁The trunk mesoderm of a neurula-stage embryo can be subdivided into four regions alon

34、g the dorso-ventral axis 第35頁/共63頁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 mesoderm) is controlled by the gradient of BMP4 signaling. High doses of BMP4 activ

35、ate 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 through activating myf5 et al The mesoderm becomes notochord tissue when no BMP4 activ

36、ity is present in the most dorsal region第36頁/共63頁The antero-posterior axial patterning in vertebratesPatterning of the vertebrate embryo along the AP axis will be focused on:Patterning of the dorsal mesoderm that forms the somites, the blocks of mesodermal cells that give rise to the skeleton and mu

37、scles of the trunkPatterning of the ectoderm that will develop into the nervous system. 第37頁/共63頁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 Drosophila

38、1.3 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 system2.4 Specifying the left-right axis (left-right asymmetry o

39、f internal organs)第38頁/共63頁Neural tube and somites seen by scanning electron microscopy第39頁/共63頁Patterning of the somite-forming mesoderm along the antero-posterior axisn Somites are blocks of mesodermal tissue that are formed after gastrulation. They forms sequentially in pairs on either side of th

40、e 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 AP axis. The anterior-most

41、somites skullThose posterior to them cervical vertebraeMore posterior ones thoracic vertebrae with ribs第40頁/共63頁n The pre-somatic mesoderm is patterned along its AP axis before somite formation begins during gastrulation.n The positional identity of the somites is specified by the combinatorial expr

42、ession 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 corresponding to their order in the cluster along the chromosomen Mutations or overexpression of a Hox gene results, in general, in localized def

43、ects in the region in which the gene is expressed, and cause homeotic transformations（同源異型轉化同源異型轉化）.Somites are formed in a well-defined order along the antero-posterior axis第41頁/共63頁Specification of the pre-somitic mesoderm by position along the antero-posterior axis has occurred before somite form

44、ation begins during gastrulation 第42頁/共63頁Identity of somites along the antero-posterior axis is specified by Hox gene expression (I)n The Hox (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

45、 as the homeodomain. The homeodomain is encoded by a DNA motif of around 180 base pairs termed the homeobox, a name that came originally from the fact that this gene family was discovered through mutations that produce a homeotic transformationa mutation in which one structure replaces another. For

46、example, the four-winged fly. n Hox genes that specify positional identity along the AP axis were originally identified in Drosophila and it turned out that related genes are involved in patterning the vertebrate axis 第43頁/共63頁Identity of somites along the antero-posterior axis is specified by Hox g

47、ene expression (II)n All the Hox genes whose functions are known encode transcriptional factors. Most vertebrates have four separate 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

48、and spatial order that reflects their order on the chromosome. That is-a spatial pattern of genes on a chromosome corresponds to 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 Th

49、e overall pattern suggests that the combination of Hox genes provides positional identity for each somite. In the cervical region, for example, each somite, and thus each vertebra, could be specified by a unique pattern of Hox gene expression 第44頁/共63頁Specification of the identity (characteristic st

50、rucutre) of each segment is accomplished by the homeotic selector (同源異型選擇者同源異型選擇者) geneslab and Dfd-the head segmentsScr 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 gene

51、s encoding the Antennapedia and bithorax complexes第45頁/共63頁Loss-of-function mutations in the Ultrabithorax gene can transform the 3rd thoracic segment into another 2nd thoracic segment, producing a four-winged fly 第46頁/共63頁第47頁/共63頁第48頁/共63頁Almost every region in the mesoderm along the antero-poster

52、ior axis is characterized by a particular set of expressed Hox genes第49頁/共63頁第50頁/共63頁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 Pattern

53、ing 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 system2.4 Specifying the left-right axis (left-right asymmetry of internal

54、organs)第51頁/共63頁The ectoderm lying 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頁/共63頁第53頁/共63

55、頁Rhombomere: 菱腦節(jié)Branchial arches: 鰓弓第54頁/共63頁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 identiti

56、es of both rhombomeres (菱腦節(jié)) 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 hindb

57、rain. Thus, the Hox genes determine patterning of the hindbrain region along the AP axis第55頁/共63頁第56頁/共63頁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 tissues of the mouset

58、he 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 overlapping domains in the developing forebrain and hindbrain,