2009 Lecture 2

Cell Division and Fertilization

This lecture will introduce two key concepts of biology, cell division and cellular sexual development.

Cell Division

Historic Historic 1882 mitosis drawings

Introduction

How does one cell become two?

Movies

• JCB - Movie Collection Mitosis | Cytokinesis

• 2008 ANAT3231 Lecture PDF lecture14-15 1 slide/page (view) | 4 slides/page (print) | 6 slides/page (print) | text (print)

Cell Division

• Cell Division Milestones
• Recent Nobel Prizes

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

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

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

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

UNSW Embryology Links

• Lecture 2 2008
• ANAT3231 Cell Division

Next Lecture

Lecture 3 | Course Timetable

Dr Mark Hill 2009 UNSW CRICOS Provider Code No. 00098G