Cell Differentiation Flashcards
how cell development occurs
- all cells contain the same genes
- “genes are not gained or lost in the normal course of development”
- rather their expression is controlled
- Different cell types express different sets of proteins (differentiation)
development
- In multi-cellular organisms, life begins as a single cell.
- With few exceptions, somatic cells contain the same genetic information as the zygote.
- In development, cells commit to specific fates & differentially express subsets of genes.
- Cells identify and respond to their position in developmental fields.
- Daughter cells may differ with respect to regulatory instructions and developmental fate.
cell differentiation –> specialisation
- A cell changes or differentiates to carry out specialised functions
- Often marked by a change in cell appearance – morphology
- Differentiated cells produce specific proteins
- Differentiation is usually preceded by rapid proliferation
- Differentiation is a DNA-orchestrated set of cellular changes that normally occurs without error*
- Differential gene expression from the same nuclear repertoire
- Accomplished by regulation of gene expression at several levels
(phenotype: physical appearance of the cell)
cells, tissues & organs
- Cell fate and differentiation are patterned in space (special)
- Also involves the intricate patterning & timing (temporal) of cell proliferation (temporal)
- Activation of cell division in some regions
- Imposition of cell cycle arrest in others ∴ controlled in a spatio-temporal manner
- The cell cycle, its control & checkpoints are of major importance in differentiation & development
- Cells not only have to proliferate & differentiate
- Sort into different tissues
- Segregate within tissues to form compartment boundaries
cell asymmetry
Early Mammalian Development
- Symmetric division yields identical daughter cells that may have different fates if exposed to different external signals.
- Asymmetric cell division yields two different types of daughter cells with different fates.
- Mammalian embryo initial divisions yield equivalent totipotent cells;
- subsequent divisions give rise to the blastocyst inner cell mass and surrounding trophectoderm as the first differentiation event.
building the embryo
Developmental decisions:
o made at specific times during development
o many are binary (yes/no), e.g., male or female
o most are irreversible
o many involve groups of cells rather than single cells
In animals decisions are made to:
o establish anterior-posterior and dorsal-ventral axes
o subdivide anterior-posterior axis into segments
o subdivide dorsal-ventral axis into germ layers
o produce various tissues and organs
- Most decisions involve changes in transcription
developmental strategy
- Mother deposits material (mRNA and protein) that creates asymmetries - set up gradients that broadly define areas (basic body plan map!)
- Gene interaction subdivides these areas (cells differentiate)
- These identities are remembered
features of cell polarity and asymmetric cell division (Common hierarchy of steps in generating a polarized cell before cell division)
- Cells exposed to a spatial cue – soluble signals from other cells/ECM
- Closest cell receptors bind extracellular signaling molecules
- Cell receptors locally activate an intracellular signaling pathway.
- Signaling pathway directs organization/orientation of the cytoskeleton (microtubules and/or microfilaments, depending on the system).
- Polarized cytoskeleton transports membrane-trafficking organelles and macromolecular complexes including fate and polarity determinants to one end of cell.
- Polarity –
o Reinforced by return of polarity determinants that have moved away from the site of concentration
o May involve endocytosis of membrane proteins and transport back to polarity site
(b) Cell polarity determinants – mRNAs, proteins, and lipids:
o Asymmetrically localized in mother cell
o Mitotic spindle – positioned so that polarity determinants are segregated differentially into daughter cells during cell division
role of cytoskeleton in development
- Consists of highly organized rods and fibers
o microfilaments (actin)
o intermediate filaments
o microtubules - Such structures are polar, with distinct “+” and “–” ends
- Serve as highway system for intracellular transport
- Asymmetry of cytoskeletal elements plays fundamental roles
o directed transport of molecules - Cytoskeletal components give directional information - through orientation of filaments
- Multiple independent trafficking system … different cell components moved
tissue identity
- Gradients of differentiation factors define a coordinated system for the entire embryonic body, then axial subunits such as limb buds
o Axial orientation (head /tail & anterior/posterior)
o Homeo-box genes (patterning)
o Dorso-ventral identity
differentiation
The development of specialised cells/tissues recognised morphologically
- differentiated cells produce specific proteins
- all genes of the genome are present in every cell BUT only a small specific number are expressed (switched on) in each cell type
the body plan
- The spatial pattern of tissues and body parts is influenced by:
o program of gene expression that specifies the pattern of the body
o local cell interactions that induce different parts of the program - The basic body plan of all animals is very similar
o preserves commonalities of molecular and cellular mechanisms controlling development - Structures during embryonic development very similar across species
patterning genes
- Encode proteins that:
o Control expression of other genes (transcription factors bind to DNA)
o Cell adhesions molecules
o Signalling molecules, morphogens & more protein kinases - All expressed in a spatio-temporal manner that permits the integration and coordination of events in the developing embryo
- The precise timing of events is maintained by one group of cells inducing differentiation in a second group
- Mediated by:
o Direct cell-cell contact
o Soluble factors released by cells (morphogens)
regulation of gene patterning
morphogen = a chemical agent able to cause or determine morphogenesis
- “genes are not gained or lost in the normal course of development”
- Therefore: Developmentally regulated and tissue specific gene expression must be very well regulated to enable differential gene expression in the right place at the right time.
differentiation, division and new cell types
- Different cells have varying abilities to divide or differentiate.
- Cells in the embryo proliferate rapidly before differentiating
- Some adult tissues contain cells with a similar capacity to proliferate and regenerate tissue. These are called somatic stem cells.
- Most adult cells have a limited capacity to divide because they lack telomerase activity.
- Telomeres shorten with cell division
- Embryonic (& tumour cells) express telomerase