III生殖细胞发生与受精PPT学习教案

1、会计学1III生殖细胞发生与受精生殖细胞发生与受精The germ cell development and fertilizationn How are the germ cells specified and determined?n How are the primordial germ cells differentiated into eggs and sperm? (including meiosis)n Fertilization and activation of the egg by the sperm that initiates the embryonic develop

2、ment. 第1页/共28页The germ cell development and fertilization1 The germ cell fate determination and development of gonads1.1 Specification and determination of the primordial germ cells (PGCs)1.2 The germ cell migration and development of gonads2 Gametogenesis2.1 Spermatogenesis2.2 Oogenesis3 Fertilizat

3、ion3.1 The recognition of egg and sperm3.2 The prevention of polyspermy3.3 The activation of egg metabolism第2页/共28页The germ cell development and fertilization1 The germ cell fate determination and development of gonads1.1 Specification and determination of the primordial germ cells (PGCs)1.2 The ger

4、m cell migration and development of gonads2 Gametogenesis2.1 Spermatogenesis2.2 Oogenesis3 Fertilization3.1 The recognition of egg and sperm3.2 The prevention of polyspermy3.3 The activation of egg metabolism第3页/共28页Specification and determination of the PGCsn Gametes in all sexually reproducing org

5、anisms arise from the primordial germ cells (PGCs)n In many instances (including nematodes, flies, and frogs ), the PGCs are specified and determined autonomously by the cytoplasmic determinants in the egg that are comprised of specific proteins and mRNAs. These cytoplasmic determinants are collecti

6、vely referred to as the germ plasm（生殖质生殖质）n Germ plasm can be identified morphologically by the presence of conspicuous membrane-unbound organelles with an electron-dense granulofibrillar appearance called germ granulesP granules in C. elegansPolar granules in DrosophilaGerminal granules in Xenopus第

7、4页/共28页The germ cell fate of C. elegans is determined at the 16-cell embryo第5页/共28页The adult gonads and early development of the fertilized egg in C elegans第6页/共28页The cell lineage chart in the development of C elegans558 cells present in the newly hatched larva, 959 somatic cells in the adult第7页/共2

8、8页Origin of the PGCs in Drosophilan In Drosophila, the PGCs form as a group of pole cells at the posterior pole of the cellularizing blastoderm. The pole plasm （极质极质）at the posterior pole is critical for determination of the PGCs in flies. n The pole plasm includes several components that are crucia

9、l for the PGC determination. Those are mRNA of gcl (germ cell less) gene, Oskar, Nanos, Vasa, mitochondrial ribosomal RNA (mtr RNA) etc.第8页/共28页Origin of the PGCs in DrosophilaThe PGCs known as pole cells become distinct at the posterior pole of the egg about 90 minutes after fertilization. The cyto

10、plasm at the posterior pole is called pole plasm and is distinguished by large organelles, the polar granules, which contains both proteins and mRNAs第9页/共28页第10页/共28页The molecular mechanisms underlying the specification and determination of the PGCs in Drosophila (I)n In Drosophila, the PGCs form as

11、 a group of pole cells at the posterior pole of the cellularizing blastoderm. The pole plasm （极质极质）at the posterior pole is critical for determination of the PGCs in flies. The pole plasm includes several components that are crucial for the PGC determination. Those are mRNA of gcl (germ cell less) g

12、ene, Oskar, Nanos, Vasa, mitochondrial ribosomal RNA (mtr RNA) etc.第11页/共28页n In Drosophila, several maternal gene (at least 8 genes) are functionally necessary and sufficient for the pole plasm formation, and the germ cell specification/determination oskar, result in the affected homozygous individ

13、ual being “grandchildless”. Its offsprings (F1) lack a proper pole plasm, and although they may develop normally in other ways, they lack germ cells and therefore are sterile (F2).Expression of oskar alone is sufficient for ectopically specifying the germ cellsThe molecular mechanisms underlying the

14、 specification and determination of the PGCs in Drosophila (II)第12页/共28页The gene oskar is sufficient to specify the germ cells in Drosophila第13页/共28页Functionally conserved genes in Germ-Cell Development 第14页/共28页Origin of the PGCs in mammalsn There is no obvious germ plasm in mammals, and mammalian

15、germ cells are not morphologically distinct during early development. Rather, germ cells are induced in gastrulating embryos n In mice, the germ cells form at the posterior region of the epiblast, at the junction of the extraembryonic ectoderm, epiblast, primitive streak, and allantois. 第15页/共28页The

16、 mammalian PGCs appear to be induced in the early gastrulating embryos第16页/共28页The molecular mechanisms underlying the specification and determination of the PGCsn There is no evidence for germ plasm being involved in germ cell formation in the mouse or other mammals. Instead, germ cell specificatio

17、n in the mouse involves cell-cell interactions. n In mice, At day 6.5 of embryonic development, BMP4 and BMP8b from the extraembryonic ectoderm give certain cells in this area the ability to produce germ cells.第17页/共28页Germ cell specification in the mouse involves cell-cell interactions Germ-cell fo

18、rmation in the mouse. The precursors (white) of primordial germ cells (PGCs) and extra-embryonic mesoderm are induced in the proximal epiblast by signals from the extra-embryonic ectoderm that include BMP-4. During gastrulation, these cells move to the posterior end of the embryo above the primitive

19、 streak. Here they form a cluster in which the central cells becomes specified as PGCs and the peripheral cells as extra-embryonic mesoderm. After their formation, the PGCs migrate to the gonads.第18页/共28页BMP4 is required for the generation of primordial germ cells in the mouse embryosA: Wild type em

20、bryo; B: High magnification of part of A showing individual PGCs in the hindgut; C: Embryos heterozygous for BMP4 mutant. There are fewer PGCs compared with the wild type; D: Homozygous embryo. PGCs are entirely absent in the hindgut第19页/共28页The germ cell development and fertilization1 The germ cell

21、 fate determination and development of gonads1.1 Specification and determination of the primordial germ cells (PGCs)1.2 The germ cell migration and development of gonads2 Gametogenesis2.1 Spermatogenesis2.2 Oogenesis3 Fertilization3.1 The recognition of egg and sperm3.2 The prevention of polyspermy3

22、.3 The activation of egg metabolism第20页/共28页n In many animals, germ cells develop at some distance from the gonads, and only later migrate to them, where they differentiate into eggs and sperm. n In the mouse gastrula, germ cells first become detectable at the posterior region of the epiblast（上胚层上胚层

23、）. They become incorporated into the hindgut and then move from gut tube into the genital ridge.n The mechanisms by which the PGCs know the route of migrating journey is still unknown. Fibronectin is likely to be an important substrate for PGC migration. In vitro evidence suggests that TGF-beta like

24、 protein is capable of attracting mouse PGCs. n 2 genes, White spotting (W) and Steel, are involved in controlling proliferation of migrating germ cells. Germ cell migration and the underlying mechanisms (I)第21页/共28页n In Drosophila, the PGCs move from the posterior pole to the gonads in a manner sim

25、ilar to that of mammalian germ cells.n The wunen gene appears to be responsible for directing the migration of the PGCs from the endoderm to the mesoderm; 2 genes, columbus and hedgehog, appear to be critical for the attracting the Drosophila PGCs to the gonads.Germ cell migration and the underlying

26、 mechanisms (II)第22页/共28页Pathway for the migration of mammalian PGCs第23页/共28页Gonads in mouse embryos at day 13.5 stained with antibodies to E-cadherin (red) and laminin (green)Proliferation of PGCs from an initial population of 10-100 cells to 2500-5000 cells in the gonads by day 12 of mouse embryosNote: The PGCs of both sexes express high levels of E-cadherin and are arranged in cortical clusters in the ovary and in internal cord in the testes