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Fertilization, cell proliferation and differentiation www.sciencepicturecompany.com Molecular Cell Gene-cs 416451 Mingkwan Nipitwa6anaphon folliculogenesis = a maturation of the ovarian follicle Overian follicle is a densely packed shell of somatic cells that contains an immature oocyte. Order of changes in ovary. 1 - Menstruation 2 - Developing follicle 3 - Mature follicle 4 - Ovulation 5 - Corpus luteum 6 - Deterioration of corpus luteum h6ps://en.wikipedia.org/wiki/Folliculogenesis folliculogenesis h6ps://en.wikipedia.org/wiki/Folliculogenesis spermatogenesis Production of Spermatozoa from primodial germ cells - Used both mitosis and meiosis h6ps://en.wikipedia.org/wiki/Spermatogenesis Spermatidogenesis • Creation of spermatid from secondary spermatocytes Spermiogenesis • Maturation of spermatid into mature spermatozoa Spermiation • Releasing of mature spermatozoa from Sertoli cells to the lumen of seminiferous tubules Spermiogenesis • Maturation of spermatid into mature spermatozoa • 4 stages – Golgi phase • change from radially symmetrical shape to become more polarity shape • head formation at one end and Golgi apparatus create acrosome, the other end mitochondrial gather and distal centriole form axoneme • DNA is densely packed --> transcriptionally inactive – Cap phase / acrosome phase • Golgi apparatus becoming acrosomal caps – Formation of tail – Maturation stage • Access cytoplasm is phagocytosed by Sertori cells in the testes Spermiogenesis h6ps://en.wikipedia.org/wiki/Spermiogenesis Maturation stage Access cytoplasm is phagocytosed by Sertori cells in the testes h6ps://en.wikipedia.org/wiki/Spermatogenesis fertilization • Fusion of 2 haploid gametes to become diploid zygote – Internal fertilization – External fertilization • Involved in many signaling processes and cell division • In animals, there must be mechanisms to prevent polyspermy – in mammals, the "cortical reaction" modifies the extracellular coat of the egg (the zona pellucida), and additional mechanisms modify the egg's plasma membrane fertilization • When the sperm bind to the egg before fertilization, the egg become metabolically active – Lots of transcription, translation and protein synthesis • The fusion of the sperm to the egg continues the meiotic process resulting in the releasing of polar nuclei fertilization • Fertilization is completed when there is a formation of pronuclei • Also called a "zygote", "1 cell embryo" or "2 pronuclei embryo" h6p://www.advancedfer-lity.com/fer-liza-on.htm fertilization en.wikipedia.org fertilization Click to see fertilization video link h6p://bit.ly/1F7gaxd h6p://humanphysiology2011.wikispaces.com/ fertilization Proliferation • Cleavage - Rapid cell division • Gastrulation - Cell movements and 3 layers form – Ectoderm – Mesoderm – Endoderm • Organogenesis – Pattern formation – Cell differentiation • Endoderm -> digestive tract • Mesoderm -> support tissues, e.g. skeleton, muscle, connective tissues, blood, urogential system • Ectoderm - > epidermis, nervous system www.stemcure.com Differentiation • A process by which individual cells become specialized and distinct from other groups of cells • Change in cell’s size, shape, membrane potential, metabolic activity, responsiveness to signals • Differentiation occurs at various stage of development but mostly after fertilization Different ways of differentiation Determination & differentiation • Determination = the process of establishing which genes will be expressed and which will not. • Cells progressively lose their genetic capacity (genes, or chromosomes) during the development à cells become determined? • In fact, determination is regulated by gene expression h6p://biology.kenyon.edu/courses/biol114/Chap11/Chapter_11.html Asymmetric segregation determines the cell type Asymmetric segregation of cellular determinants is based on the asymmetric localization of cytoplasmic molecules (usually proteins or mRNAs) within a cell before it divides. During cell division, one daughter cell receives most or all of the localized molecules, while the other daughter cell receives less (or none) of these molecules. This results in two different daughter cells, which then take on different cell fates based on differences in gene expression. The localized cytoplasmic determinants are often mRNAs encoding transcription factors, or the transcription factors themselves. h6p://biology.kenyon.edu/courses/biol114/Chap11/Chapter_11.html Control of gene activity • RNA level – Transcription regulation - epigenetics – RNA processing – RNA transport – Selection of mRNA for translation – mRNA degradation • Protein level – Translational control – Protein modification – Protein degradation mRNA processing apbio-‐werle.wikispaces.com mRNA degradation Specialized cells in different tissues have large amount of certain mRNAs Fraction No. Of different mRNAs Copies per cell % of total mRNAs Oviduct I 1 100,000 50 II 8 3,750 15 III 14,000 5 35 I 1 32,800 16 II 106 750 40 III 11,600 7 44 Liver Fraction I = highly abundant Fraction II = moderately abundant Fraction III = rare Ex. Despite Cell A and B have iden-cal gene-c materials, there are some genes that expressed only in Cell type A or Cell type B, but many of them can s-ll share the same expression pa6erns. Thus, different types of cells expressed genes differently. Cell A 17 Cell B 179 25 Housekeeping gene products "luxury gene products", presen-ng specific developmental program h6p://biology.kenyon.edu/courses/biol114/Chap11/Chapter_11.html Cell potency • Developmental potency = ability of cell to develop into different cell types – Unipotency – pluripotency – totipotency h6p://163.16.28.248/bio/ac-velearner/16/ch16c4.html Pluripotency: stem cells can differentiate into many blood cell types h6ps://en.wikipedia.org/wiki/File:Hematopoiesis_(human)_diagram.png Types of blood cells • White blood cells (leucocytes) – Neutrophils – most abundant, 40-75% of WBC • Innate (non-specific) immune system • polymorphonuclear cells (PMNs), contain various cytotoxic substance • phagocytic – Basophils – least common, 0.01-0.3% of WBC • e.g. mast cells – store histamine • Parasitic infection and allergy function – Eosinophils – 1-6% of WBC • combating multicellular parasites • associated with allergy and asthma (หอบหืด) Types of blood cells • White blood cells (leucocytes) – Monocytes – largest types of leucocyte, 2-10% of WBC • Unilobal nuclear, like amoeba • eplenishing resident macrophages • response to inflammation signals from sites of infection in the tissues • differentiation into macrophages or dendritic cells to effect an immune response – Lymphocytes Types of blood cells • White blood cells (leucocytes) – Lymphocytes • Thymus (T)-cell – T helper cell – release cytokines and growth factors that regulate other immune cells – T cytotoxic cell – lysis of virally infected cells, tumour cells and allografts • Bone marrow (B)-cell – secrete antibody • Natural killer (NK) cell – lysis of virally infected cells and tumour cells Regeneration • A process of renewal, restora-on, and growth to repair the damage or maintain physiological and morphological stages • Regulated by a sexual cellular process snowbio.wikispaces.com psi.wikia.com www.tutorvista.com Pattern formation • Cells need to know what they are and what they do • A local group of cells organize into a pattern of different cell types – Need communication between cells by chemical signal – The signal can vary in concentrations (gradient) resulting in different fate of cells morphogen • A special type of chemical signal that specifies development of particular pattern • There is a threshold of the morphogen – Reach the threshold -> cell become determined -> differentiate Threshold 1 à cell differen-ates into type 1 Threshold 2 à cell differen-ates into type 2 Threshold 3 à cell differen-ates into type 3 h6p://biology.kenyon.edu/courses/biol114/Chap11/Chapter_11.html Pattern formation In Drosophila embryo development Bicoid = a transcription factor that acts as a morphogen gradient Bicoid is enriched in the anterior part of the embryo resulting in differential levels of other transcriptional factors, e.g. hunchback, tailess, empty spiracles, Kupppel h6p://biology.kenyon.edu/courses/biol114/Chap11/Chapter_11.html Pattern formation Pattern formation h6p://plantdev.bio.wzw.tum.de/index.php?id=58 Mutation of the homeobox (transcriptional factor) result in developmental abnormality: antenapedia (fly that have legs where the antena should be Eyeless is a transcription factor eyeless mutant has no eye while overexpression of this gene results in developing eyes at the legs www.gehring.biozentrum.unibas.ch www.scienceforums.net Dedifferentiation • A cellular process that differentiated cells reverts to the earlier developmental stage – Ex. worms and amphibians in which a partially or terminally differentiated cell reverts to an earlier developmental stage, usually as part of a regenerative process. Dedifferentiation also occurs in plants. • Cells in cell culture can lose properties they originally had, such as protein expression, or change shape. This process is also termed dedifferentiation. • Dedifferentiation can be an aberration of the normal development cycle that results in cancer • A small molecule dubbed reversine, a purine analog, has been discovered that has proven to induce dedifferentiation in myotubes. These dedifferentiated cells could then redifferentiate into osteoblasts and adipocytes. levels of differentiations in cancer cells • Grade 1: well differentiated cancer cells, look a lot like normal cells, slow growing. • Grade 2: moderately differentiated, do not look like normal cells, growing faster than normal cells. • Grade 3: poorly differentiated, do not look like normal cells, fast-growing or “aggressive.” h6p://gcmaf.-msmithmd.com/book/chapter/60/ Terminal differentiation • Cells specilized • Post mitotic (stop dividing) -> die • Sometimes cell dead is a part of differentiation, e.g. Progressive keratinization of skin cell, progressive lignification of xylogenic cells Click to see keratnization video link h6p://bit.ly/1Dkf4cN