Talk:2009 Lecture 2

From Embryology

PMID: 18753611

"Whether or not oogenesis continues in the ovaries of mammalian females during postnatal life was heavily debated from the late 1800s through the mid-1900s. However, in 1951 Lord Solomon Zuckerman published what many consider to be a landmark paper summarizing his personal views of data existing at the time for and against the possibility of postnatal oogenesis. In Zuckerman's opinion, none of the evidence he considered was inconsistent with Waldeyer's initial proposal in 1870 that female mammals cease production of oocytes at or shortly after birth. This conclusion rapidly became dogma, and remained essentially unchallenged until just recently, despite the fact that Zuckerman did not offer a single experiment proving that adult female mammals are incapable of oogenesis. Instead, 20 years later he reemphasized that his conclusion was based solely on an absence of data he felt would be inconsistent with the idea of a nonrenewable oocyte pool provided at birth. However, in the immortal words of Carl Sagan, an "absence of evidence is not evidence of absence." Indeed, building on the efforts of a few scientists who continued to question this dogma after Zuckerman's treatise in 1951, we reported several data sets in 2004 that were very much inconsistent with the widely held belief that germ cell production in female mammals ceases at birth. Perhaps not surprisingly, given the magnitude of the paradigm shift being proposed, this work reignited a vigorous debate that first began more than a century ago. Our purpose here is to review the experimental evidence offered in recent studies arguing support for and against the possibility that adult mammalian females replenish their oocyte reserve. "Never discourage anyone who continually makes progress, no matter how slow."-Plato (427-347 BC)."


Cell Division

Historic 1882 mitosis drawing.jpg

Historic Historic 1882 mitosis drawings

Introduction

How does one cell become two?

Movies


MH - Due to yesterday's fire alarm we will complete Cell Cycle lecture in the Lab on Thursday.

Please use the 2008 course slides linked below for Cell Division content (this current page content has not yet been edited/completed).

Cell Division

Features 2 mechanical processes

  • Mitosis segregation of chromosomes and formation of 2 nuclei
  • Cytokinesis splitting of the cell as a whole into 2 daughter cells

Cell Changes

  • Nucleus
    • Chromosome condensation
    • Nuclear envelope breakdown
  • Cytoplasm
    • Cytoskeleton reorganization
    • Spindle formation (MT) Contractile ring (MF)
    • Organelle redistribution

Mitosis Phases

  • Based on light microscopy of living cells light and electron microscopy of fixed and stained cells
  • 5 Phases - prophase, prometaphase, metaphase, anaphase, and telophase
    • Cytokinesis 6th stage overlaps the end of mitosis

Movie: Cell Division Animation

Cell Cycle

Overview

Mitosis- Interphase Not a mitotic phase (discussed in cell cycle) Chromosomes dispersed in nucleus Gene expression Cytoskeleton and cell organelles Distributed and functioning Mitochondria undergo independent proliferation/division

Chromosome Changes

Mitosis fl.jpg

Prophase

  • Chromosome DNA has been earlier duplicated (S Phase)
  • Chromosomes begin condensing
  • Chromosome pairs (chromatids) held together at centromere
  • Microtubules disassemble
  • Mitotic spindle begins to form

At end of prophase nuclear envelope breaks down

Prometaphase

  • Microtubules now enter nuclear region
  • Nuclear envelope forms vesicles around mitotic spindle
  • Kinetochores form on centromere attach to some MTs of spindle

At end of prometaphase chromosomes move to metaphase plate

Movie: Embryo Mitosis

Movie: Astral Microtubules Microtubule Organisation

Movie: Microtubules Mitotic Spindle

Kinetochore

Kinetochore Movement Movie: Mitotic Spindle- Kinetochore

Metaphase

  • Kinetochore MTs align chromosomes in one midpoint plane

Metaphase ends when sister kinetochores separate

Anaphase

Chromosome motility anaphase
  • Separation of sister Kinetochores
  • shortening of Kinetochore microtubules pulls chromosome to spindle pole

Anaphase ends as nuclear envelope (membrane) begins to reform

Two telophase HeLa cells expressing GFP–tagged human Aurora B Microtubules - red inner-centromere protein - blue Aurora B–GFP - green DNA - white

Telophase

  • Chromosomes arrive at spindle poles
  • Kinetochore MTs lost
  • Condensed chromosomes begin expanding
    • Continues through cytokinesis

Cytokinesis

  • Division of cytoplasmic contents
  • Contractile ring forms at midpoint under membrane
  • Microfilament ring Contracts forming cleavage furrow
  • Eventually fully divides cytoplasm


Cell Organelles

Mitochondria

  • Divide independently of cell mitosis
  • distributed into daughter cells

Peroxisomes

  • localise at spindle poles

Endoplasmic Reticulum

Golgi

File:Post-mitotic Golgi stack formation.png
Post-mitotic Golgi stack formation
  • 2 processes - disassembly and reassembly
  • Golgi stack undergoes a continuous fragmentation process
  • fragments are distributed into daughter cells
  • are reassembled into new Golgi stacks

Disassembly

  • Unstacking - mediated by two mitotic kinases (cdc2 and plk)
  • Vesiculation - mediated by COPI budding machinery ARF1 and the coatomer complex

Reassembly

  • Fusion - formation of single cisternae by membrane fusion
  • Restacking - requires dephosphorylation of Golgi stacking proteins by protein phosphatase PP2A

Links: Tang D, Mar K, Warren G, Wang Y. Molecular mechanism of mitotic Golgi disassembly and reassembly revealed by a defined reconstitution assay. J Biol Chem. 2008 Mar 7;283(10):6085-94. Epub 2007 Dec 21. PMID: 18156178

Mitosis and Meiosis

Mitosis meiosis1.jpg Progeny

Mitosis 2 Daughter cells identical to parent (diploid)

Meiosis Germ cell division (haploid)

  • Reductive division
  • Generates haploid gametes (egg, sperm)
  • Each genetically distinct from parent
  • Genetic recombination (prophase 1)
    • Exchanges portions of chromosomes maternal/paternal homologous pairs
  • Independent assortment of paternal chromosomes (meiosis 1)

Cell Birth - Mitosis and Meiosis 1st cell division- Meiosis

Homologous chromosomes pairing unique to meiosis

  • Each chromosome duplicated and exists as attached sister chromatids before pairing occurs
  • Genetic Recombination shown by chromosomes part red and part black
    • chromosome pairing in meiosis involves crossing-over between homologous chromosomes

(For clarity only 1 pair of homologous chromosomes shown)

Comparison of Meiosis/Mitosis

  • After DNA replication 2 nuclear (and cell) divisions required to produce haploid gametes
  • Each diploid cell in meiosis produces 4 haploid cells (sperm) 1 haploid cell (egg)
  • Each diploid cell mitosis produces 2 diploid cells

Abnormalities

Meiotic Nondisjunction

  • Occurs when homologues fail to separate during meiotic division I or II
  • Down Syndrome
  • Caused by an extra copy of chromosome 21

Chromosomal Translocations

  • Philadelphia chromosome
  • Chronic myelogenous leukemia
    • Piece of Chr9 exchanged with Chr22 Generates truncated abl

Overstimulates cell production

Meiosis Sex Differences

Female (oogenesis)

  • Meiosis initiated once in a finite population of cells
  • 1 gamete produced / meiosis
  • Completion of meiosis delayed for months or years
  • Meiosis arrested at 1st meiotic prophase and reinitiated in a smaller population of cells
  • Differentiation of gamete occurs while diploid in first meiotic prophase
  • All chromosomes exhibit equivalent transcription and recombination during meiotic prophase

Male (spermatogenesis)

  • Meiosis initiated continuously in a mitotically dividing stem cell population
  • 4 gametes produced / meiosis
  • Meiosis completed in days or weeks
  • Meiosis and differentiation proceed continuously without cell cycle arrest
  • Differentiation of gamete occurs while haploid after meiosis ends

Sex chromosomes excluded from recombination and transcription during first meiotic prophase

References

Textbooks

Essential Cell Biology

  • Essential Cell Biology Chapter 17

Molecular Biology of the Cell

Alberts, Bruce; Johnson, Alexander; Lewis, Julian; Raff, Martin; Roberts, Keith; Walter, Peter New York and London: Garland Science; c2002

Molecular Cell Biology

Lodish, Harvey; Berk, Arnold; Zipursky, S. Lawrence; Matsudaira, Paul; Baltimore, David; Darnell, James E. New York: W. H. Freeman & Co.; c1999

The Cell- A Molecular Approach

Cooper, Geoffrey M. Sunderland (MA): Sinauer Associates, Inc.; c2000

Search Online Textbooks

Books

PubMed

  • PubMed is a service of the U.S. National Library of Medicine that includes over 18 million citations from MEDLINE and other life science journals for biomedical articles back to 1948. PubMed includes links to full text articles and other related resources. PubMed
  • PubMed Central (PMC) is a free digital archive of biomedical and life sciences journal literature at the U.S. National Institutes of Health (NIH) in the National Library of Medicine (NLM) allowing all users free access to the material in PubMed Central. PMC
  • Online Mendelian Inheritance in Man (OMIM) is a comprehensive compendium of human genes and genetic phenotypes. The full-text, referenced overviews in OMIM contain information on all known mendelian disorders and over 12,000 genes. OMIM
  • Entrez is the integrated, text-based search and retrieval system used at NCBI for the major databases, including PubMed, Nucleotide and Protein Sequences, Protein Structures, Complete Genomes, Taxonomy, and others Entrez

Search Pubmed

Reviews

  • The great divide: coordinating cell cycle events during bacterial growth and division. Haeusser DP, Levin PA. Curr Opin Microbiol. 2008 Apr;11(2):94-9. Epub 2008 Apr 7. Review. PMID: 18396093 | PMC
  • Cell cycle studies based upon quantitative image analysis. Stacey DW, Hitomi M. Cytometry A. 2008 Apr;73(4):270-8. Review. PMID: 18163464
  • Analysis of cell cycle phases and progression in cultured mammalian cells. Schorl C, Sedivy JM. Methods. 2007 Feb;41(2):143-50. Review. PMID: 17189856
  • Cell cycle regulation of DNA replication. Sclafani RA, Holzen TM. Annu Rev Genet. 2007;41:237-80. Review. PMID: 17630848

Articles

TGFBeta signaling. Molecular Cell Biology -> Cancer -> Mutations Causing Loss of Cell-Cycle ControlCurrent models of the intracellular pathways leading to cell death by apoptosis or to trophic factor-mediated cell survival in mammalian cells. Molecular Cell Biology -> Cell Interactions in Development -> Cell Death and Its RegulationTGFBeta signaling pathway. Molecular Cell Biology -> Integrating Cells into Tissues -> Cell-Cell Adhesion and CommunicationOrigin of the resting potential in a typical vertebrate neuron. Molecular Cell Biology -> Cell-to-Cell Signaling: Hormones and Receptors -> From Plasma Membrane to NucleusElevation of cytosolic Ca2 via the inositol-lipid signaling pathway. Molecular Cell Biology -> Cell-to-Cell Signaling: Hormones and Receptors -> MAP Kinase Pathways

Activation of adenylyl cyclase following binding of an appropriate hormone (e.g., epinephrine, glucagon) to a Gs protein - coupled receptor. Molecular Cell Biology -> Cell-to-Cell Signaling: Hormones and Receptors -> Identification and Purification of Cell-Surface Receptors

Common intracellular signaling proteins. Molecular Cell Biology -> Cell-to-Cell Signaling: Hormones and Receptors -> Overview of Extracellular Signaling


Proposed alternative mechanisms for chromosome congression. Molecular Cell Biology -> Cell Motility and Shape II: Microtubules and Intermediate Filaments -> Microtubule Dynamics and Motor Proteins during Mitosis

Centromeric attachment of microtubules. Molecular Cell Biology -> Cell Motility and Shape II: Microtubules and Intermediate Filaments -> Microtubule Dynamics and Motor Proteins during Mitosis

The stages of mitosis and cytokinesis in an animal cell. Molecular Cell Biology -> Cell Motility and Shape I: Microfilaments -> Cell Locomotion

The coupling of ATP hydrolysis to movement of myosin along an actin filament. Molecular Cell Biology -> Cell Motility and Shape I: Microfilaments -> Myosin: The Actin Motor ProteinThe three phases of G-actin polymerization in vitro. Molecular Cell Biology -> Protein Sorting: Organelle Biogenesis and Protein Secretion -> Insertion of Membrane Proteins into the ER MembraneSynthesis of secretory proteins on the rough ER. Molecular Cell Biology -> Protein Sorting: Organelle Biogenesis and Protein Secretion -> Overview of the Secretory PathwayOverview of sorting of nuclear-encoded proteins in eukaryotic cells. Molecular Cell Biology -> Cellular Energetics: Glycolysis, Aerobic Oxidation, and Photosynthesis -> Photosynthetic Stages and Light-Absorbing PigmentsModel of the structure of ATP synthase (the F0F1 ATPase complex) in the bacterial plasma membrane. Molecular Cell Biology -> Cellular Energetics: Glycolysis, Aerobic Oxidation, and Photosynthesis -> Electron Transport and Oxidative PhosphorylationProposed model for operation of the two-Na/one-glucose symporter. Molecular Cell Biology -> Transport across Cell Membranes -> Active Transport by ATP-Powered PumpsTransmembrane forces acting on Na ions. Drosophila embryo and localization of their gene products within the embryo. Drosophila embryos. Molecular Cell Biology -> Regulation of the Eukaryotic Cell Cycle -> Overview of the Cell Cycle and Its ControlMechanism of action of telomerase. E. coli replication proteins at a growing fork. E. coli DNA polymerase III to DNA, thereby increasing its processivity. Molecular Cell Biology -> DNA Replication, Repair, and Recombination -> The DNA Replication MachineryThree mechanisms of DNA strand growth that are consistent with semiconservative replication. Molecular Cell Biology -> RNA Processing, Nuclear Transport, and Post-Transcriptional Control -> Processing of Eukaryotic mRNADiagram of interactions between pre-mRNA, U1 snRNA, and U2 snRNA early in the splicing process. Molecular Cell Biology -> RNA Processing, Nuclear Transport, and Post-Transcriptional Control -> Processing of Eukaryotic mRNAModel for cooperative assembly of an activated transcription-initiation complex at the Molecular Cell Biology-> Regulation of Transcription Initiation -> Molecular Mechanisms of Eukaryotic Transcriptional ControlModel for the packing of chromatin and the chromosome scaffold in metaphase chromosomes. Molecular Cell Biology -> Molecular Structure of Genes and Chromosomes -> Mobile DNAGeneral procedure for producing transgenic mice. Molecular Cell Biology -> Genetic Analysis in Cell Biology -> Gene Replacement and Transgenic AnimalsThe polymerase chain reaction. Molecular Cell Biology -> Recombinant DNA and Genomics -> Identifying, Analyzing, and Sequencing Cloned DNAIsolation of DNA fragments from a mixture by cloning in a plasmid vector. Molecular Cell Biology -> Recombinant DNA and Genomics -> DNA Cloning with Plasmid VectorsRetroviral life cycle. Molecular Cell Biology -> Manipulating Cells and Viruses in Culture -> Growth of Animal Cells in CultureThe synthesis and release of secretory proteins in acinar cells of the rat pancreas. Molecular Cell Biology -> Biomembranes and the Subcellular Organization of Eukaryotic Cells -> Microscopy and Cell ArchitectureModel of protein synthesis on circular polysomes and recycling of ribosomal subunits. E. coli ribosomes. Molecular Cell Biology -> Nucleic Acids, the Genetic Code, and the Synthesis of Macromolecules -> Nucleic Acid SynthesisTranscription of DNA into RNA is catalyzed by RNA polymerase, which can initiate the synthesis of strands de novo on DNA templates. Molecular Cell Biology -> Protein Structure and Function -> Purifying, Detecting, and Characterizing ProteinsSDS-polyacrylamide gel electrophoresis, a common technique for separating proteins at good resolution. Molecular Cell Biology -> Protein Structure and Function -> Folding, Modification, and Degradation of ProteinsChaperone-mediated protein folding. Molecular Cell Biology -> Chemical Foundations -> Biochemical EnergeticsCell division. Molecular Cell Biology -> The Dynamic Cell -> The Life Cycle of Cells

Links

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