Development

From CellBiology


Development

This lecture is about how the embryo makes use of cellular mechanisms (described during this term) to construct itself.

It is concerned with concepts rather than detail.

You should appreciate how these cellular mechanisms integrate to produce the whole organism.

CSt1 zygote.gif Human CST23.gif

The image above shows the first cell that forms following fertilization, and that cell's offspring 8 weeks later.

Objectives

  • Understand the utility of model organisms in research on developmental mechanisms
  • Understand the conceptual importance of somatic cell nuclear transfer (cloning) experiments
  • Understand the concept of how lineage restriction is controlled by the expression of DNA-binding transcription factors
  • Brief understanding of how transcription factor expression can be controlled by signaling pathways
  • Brief understanding of cell movements in development
  • Brief understanding of how apoptosis can create shape

Concepts

  • Cell proliferation careful control of cell division is needed to ensure that tissues achieve their correct size at the right time and in the right place.
  • Tissue differentiation - specialization of cells and expression of tissue-specific genes e.g. globin gene in blood cells.
  • Patterning - temporal and spatial expression of DNA-binding proteins e.g. the homeobox (Hox) genes.
  • Induction and cell signaling
    • Short range by cell-cell contact e.g. delta/notch
    • Long range by diffusible morphogen e.g. sonic hedgehog
  • Cell migration and shape change – cells (or parts of cells e.g. neurons) need to move through other tissues to reach the right location e.g. germ cells and limb myoblasts.
  • Morphogenesis by selective apoptosis (programmed cell death) – shapes can be created by the formation of temporary structures that are later removed by coordinated apoptosis e.g. formation of digits

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

Male and Female Meiosis

Male gametogenesis.jpg

Female gametogenesis.jpg


Links: Gametogenesis


Zygote

Zygote Formation

Chromosomal Sex Determination

Males Females
Chromosome Y Chromosome
  • 59 million base pairs, hypervariable in length, mostly non-functional repeats
  • Current known protein-coding genes = 48 including SRY
  • SRY encodes a 204 amino acid protein (TDF) that is a member of the HMG (High mobility group) box class of DNA-binding proteins. Transcription factors bind to specific sites of DNA and regulates the transcription (expression) of other genes.
Chromosome X Chromosome
  • 155 million base pairs, contains about 5% of the haploid genome and encodes house-keeping and specialized functions.
  • Genes such as Wnt-4 and DAX-1 necessary for initiation of female pathway ovary development
X inactivation]
  • one X chromosome randomly inactivated throughout the female embryo.
  • mosaic of maternal and paternally derived X chromosome activity in all tissues and organs.
Links: MBoC - Figure 20-18. Influence of Sry on gonad development

Mitosis

  • All cells formed from the zygote do so by mitosis.
  • Cell proliferation is strictly regulated
  • Unregulated/abnormal proliferation is oncogenesis or Cancer

Cell cycle1.jpg

An overview of the cell-cycle control system

Cell Cycle - External Regulators

  • Cell replacement in different tissues
    • regulated by growth factors
    • can be specific for specific cell types

Growth Factors and Cell Cycle Progress

  • External factors can also regulate progression through cycle
  • Growth factors primarily act on cells in G0 and G1
  • The restriction point is the timepoint in G1 when cells no longer respond to withdrawal of growth factors by returning to G0, but progress to S phase.
    • thought to involve retinoblastoma protein (pRb)

Restriction Point

Growth Factor Model

  • Fibroblasts in culture
    • Serum (Prepared by clotting)- Proliferation
    • Plasma (Prepared by centrifugation, no clotting)- no proliferation
  • Clotting
    • allows platelets to release secretory granules
    • Platelet-derived growth factor (PDGF)
  • Connective tissue cells express PDGF receptors which bind the small PDGF glycoprotein

Other Growth Factors

  • Interleukin-2 (IL-2)
    • Stimulates T lymphocytes
  • Nerve Growth Factor (NGF)
    • Promotes neuronal survival and growth
  • Epidermal Growth Factor (EGF)
  • Vascular Endothelial Growth Factor (VEGF)
  • Insulin-like growth factors (IFG-1, IGF-2)

Cell Cycle- Internal Regulators

  • 1980s - studies in Xenopus eggs and starfish oocytes:
  • purification of M phase-promoting factor (MPF);
  • identification of its components as cyclin B and CDC2 (also called cyclin-dependent kinase, Cell Division Cycle)

Cell cycle - Cdk cyclin.jpg

Patterning

Proposed Hox protein classification.jpg

Induction and Cell Signaling

Many developmental signals are reused at different times and different locations.

Membrane Receptors Signaling between cells, cells and matrix, tissues, and systemically, is key to the developmental and differentiation process.

Some signals final actions are as transcription factors.

Cell migration and shape change



Skeletal Muscle Stages

  • Myoblast - individual progenitor cells
  • Myotube - multinucleated, but undifferentiated contractile apparatus (sarcomere)
  • Myofibre (myofiber, muscle cell) - multinucleated and differentiated sarcomeres
    • primary myofibres - first-formed myofibres, act as a structural framework upon which myoblasts proliferate, fuse in linear sequence
    • secondary myofibers - second later population of myofibres that form surrounding the primary fibres.
  • Muscle Stem Cell - Satellite Cell

Morphogenesis by Apoptosis

Limb development

Ossification

  • Death of chondrocytes

Nervous System

  • Death of neurons
  • Disruption of Brain Development


Links: Developmental Mechanism - Apoptosis | limb - FIG5 Development - TUNEL staining

BMP syndactyly.jpg

Apoptosis in digit development

Glossary

  • Cell lineage – a linear sequence of cell fate that traces progressive states of differentiation. Analogous to the "ancestry" of a cell – e.g. liver cells are derived from the endodermal lineage.
  • Embryonic patterning – the underlying mechanism by which a shapeless ball of cells is provided with the information required to develop into its appropriate anatomical form and structure.
  • Cell commitment (specification) – the process by which a cell becomes dedicated to becoming some other more mature cell type due to its position in the embryo or as a result of its cell lineage: reversible if exposed to a different environment e.g. grafted into another location.
  • Cell determination – the process by which a cell becomes irreversibly locked into a particular cell fate: precedes differentiation. However, the cell shows no outward signs of what they are destined to be.
  • Differentiation - the process by which a less specialized cell undergoes a recognizable change (of shape and/or function) into a more specialized cell type: irreversible (under normal circumstances).
  • Morphogenesis – The overall process by which the embryo resolves itself into a mature shape



2017 Course Content

Moodle

Lectures: Cell Biology Introduction | Cells Eukaryotes and Prokaryotes | Cell Membranes and Compartments | Cell Nucleus | Cell Export - Exocytosis | Cell Import - Endocytosis | Cytoskeleton Introduction | Cytoskeleton - Microfilaments | Cytoskeleton - Microtubules | Cytoskeleton - Intermediate Filaments | Cell Mitochondria | Cell Junctions | Extracellular Matrix 1 | Extracellular Matrix 2 | Cell Cycle | Cell Division | Cell Death 1 | Cell Death 2 | Signal 1 | Signal 2 | Stem Cells 1 | Stem Cells 2 | Development | 2017 Revision

2017 Laboratories: Introduction to Lab | Fixation and Staining |


2017 Projects: Group 1 - Delta | Group 2 - Duct | Group 3 - Beta | Group 4 - Alpha

Dr Mark Hill 2015, UNSW Cell Biology - UNSW CRICOS Provider Code No. 00098G