Difference between revisions of "2009 Lecture 2"

From Embryology
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* Down Syndrome - caused by an extra copy of chromosome 21.
 
* Down Syndrome - caused by an extra copy of chromosome 21.
  
* '''Chromosomal translocations''' occur when there is an inappropriate exchange of chromosomal material.
+
* '''Chromosomal translocations''' occur when there is an inappropriate exchange of chromosomal material. [http://visualsonline.cancer.gov/retrieve.cfm?imageid=7153&dpi=72&fileformat=jpg Philadelphia chromosome]
* Philadelphia chromosome - Chronic myelogenous leukemia, piece of Chr9 exchanged with Chr22 Generates truncated abl, overstimulates cell production
+
* Philadelphia chromosome - piece of Chr9 exchanged with Chr22 Generates truncated abl, overstimulates cell production, leads to chronic myelogenous leukemia
  
 
== Fertilization ==
 
== Fertilization ==

Revision as of 17:27, 27 July 2009

Cell Division and Fertilization

This lecture will introduce two key concepts of biology, cell division and cellular sexual development. Both these concepts will also be explored further in the Thursday laboratory.

--MarkHill 15:44, 27 July 2009 (EST) Lecture notes in preparation (notice removed when complete)


Cell Cycle

The Cell Cycle
  • Cell Division (m phase) is only a brief moment in the functional life (interphase) of most eukaryotic cells.
  • The eukaryotic cell cycle is regulated by 2 protein families known as cyclins and cyclin-dependent kinases.

Cell Division

Historic drawing of mitosis

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
  • Mitosis occurs in all cells, producing genetically identical progeny.
  • Meiosis occurs only in germ cells (sperm=spermatozoa and egg=oocyte), producing genetically different progeny.
    • progeny = daughter cells, offspring


Cell Changes

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

Mitosis

Fluorescent image of Mitotic spindle and chromosomes
  • 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

Note that DNA duplication has occurred earlier in the S Phase of the cell cycle.


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
  • Prophase ends when 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
  • Prometaphase ends when chromosomes move to metaphase plate

Metaphase

  • Kinetochore MTs align chromosomes in one midpoint plane
  • Metaphase ends when sister kinetochores separate

Anaphase

  • Separation of sister Kinetochores
  • shortening of Kinetochore microtubules pulls chromosome to spindle pole
  • Anaphase ends as nuclear envelope (membrane) begins to reform

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 - associated with the nuclear envelope vesicles.
  • Golgi Apparatus- Golgi stack undergoes a continuous fragmentation process, fragments are distributed into daughter cells, then reassembled into new Golgi stacks

Meiosis

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)

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

Meiosis I and II

  • Meiosis I separates the pairs of homologous chromosomes, reduces the cell from diploid to haploid.
  • Meiosis II separates each chromosome into two chromatids (chromosome behavior in meiosis II is like that of mitosis).

Prophase I

  • The homologous chromosomes pair and exchange DNA to form recombinant chromosomes.
  • Prophase I is divided into five phases:
    • Leptotene - chromosomes start to condense.
    • Zygotene - homologous chromosomes become closely associated (synapsis) to form pairs of chromosomes consisting of four chromatids (tetrads).
    • Pachytene - crossing over between pairs of homologous chromosomes to form chiasmata (form between two nonsister chromatids at points where they have crossed over)
    • Diplotene - homologous chromosomes begin to separate but remain attached by chiasmata.
    • Diakinesis - homologous chromosomes continue to separate, and chiasmata move to the ends of the chromosomes.

Prometaphase I

  • Spindle apparatus formed, and chromosomes attached to spindle fibres by kinetochores.

Metaphase I

  • Homologous pairs of chromosomes (bivalents) arranged as a double row along the metaphase plate. The arrangement of the paired chromosomes with respect to the poles of the spindle apparatus is random along the metaphase plate. (This is a source of genetic variation through random assortment, as the paternal and maternal chromosomes in a homologous pair are similar but not identical. The number of possible arrangements is 2n, where n is the number of chromosomes in a haploid set. Human beings have 23 different chromosomes, so the number of possible combinations is 223, which is over 8 million.)

Anaphase I

The homologous chromosomes in each bivalent are separated and move to the opposite poles of the cell.

Telophase I

The chromosomes become diffuse and the nuclear membrane reforms.

Cytokinesis I

  • Cellular cytoplasmic division to form two new cells, followed by Meiosis II.

Prophase II

  • Chromosomes begin to condense, nuclear membrane breaks down and spindle forms.

Metaphase II

  • Spindle fibres attach to chromosomes, chromosomes align in cell centre.

Anaphase II

  • Chromosomes separate and move to the opposite poles of the cell.

Telophase II

  • Chromosomes reach spindle pole ends and the nuclear membrane reforms.

Cytokinesis

Cellular cytoplasmic division to form new cells.

Comparison of Meiosis/Mitosis

McGraw-Hill Animation comparing Mitosis and Meiosis

Comparison of Mitosis and Meiosis
  • 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

Meiosis Differences

  • Sex chromosomes excluded from recombination and transcription during first meiotic prophase

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

Abnormalities

Trisomy21arrow.gifTrisomy21female.jpgTrisomy21female.jpg

  • The most common chromosome abnormality is aneuploidy, the gain or loss of whole chromosomes.
  • Caused by meiotic nondisjunction, the failure of chromosomes to correctly separate homologues during meiosis I or sister chromatids during meiosis II.
  • Down Syndrome - caused by an extra copy of chromosome 21.
  • Chromosomal translocations occur when there is an inappropriate exchange of chromosomal material. Philadelphia chromosome
  • Philadelphia chromosome - piece of Chr9 exchanged with Chr22 Generates truncated abl, overstimulates cell production, leads to chronic myelogenous leukemia

Fertilization

UNSW Embryology Links

References

Textbooks

Search

Reviews

  • 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

Articles

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Lecture 3 | Course Timetable

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