Development of multicellular organisms Flashcards
multicellular development requires
- morphogenesis- generation of tissue shapes that form organ and bodies
- cell differentiation- generation of different cell types in tissues
epidermis composition
- epithelial tissue of the skin
- keratinized squames
- stem cells –> granular and prickle cell layers
- basal cell layer
dermis composition
- connective tissue of the skin
- basal lamina (specialized ECM)
- connective tissue of the dermis
embryogenesis
starts at fertilization and ends before birth
animal embryogenesis begins with
the blastocyst
- undergoes minimal morphogenesis and cell differentiation
morphogenesis requires
- internalization of cells
- elongation of the embryo
- fine re-positioning of the cells
internalization of cells
- happens during gastrulation (formation of gut tube)
- cells start crawling over the inner surface
- endoderm beginning to invaginate
- cavity formation
- future mouth and anus formed
mechanisms of cell internalization
- ingression/delamination
- individual cells separate from the early outer epithelium
- epithelial to mesenchymal transition (EMT- specialized to less specialized)
- EMT are dangerous during cancer progression - invagination/involution
- intact epithelial sheets move inside the embryo
- microtubules elongate, causing cells to become columnar
- apical actin-filament bundles contract, narrowing the cells at their apices
mechanisms of embryo elongation
- convergent extension
- converge towards center and elongate lengthwise - cell division and cell shape change
- orientation regulated by the orientation of cellulose microfibrils and driven by turgor pressure
- vertical orientation stops cells from growing vertically (short + wide)
mechanisms of cell positioning
- migration of the whole cell
- later born neurons migrate to higher cortical layers - migration of a cell extension
- attractant (netrin) binds to growth cone expressing receptor (DCC) on a commissural neuron
- growth cone expressing receptor (Roundabout, decreases netrin responsiveness and repels growth cone) for slit and semaphorin repellents
main mechanisms of cell differentiation
asymmetric- sister cells born different
symmetric- sister cells become different as result of environmental influences
asymmetric cell division
- partitions cell fate determinants to define the germline and other tissues
- requires asymmetric determinants and proper spindle alignment
- incorrect spindle alignment –> symmetrical cell division
extrinsic mechanisms of cell differentiation
- direct lateral inhibition
- cells begin equal, cells that gain an advantage differentiate and inhibit their neighbours from differentiating
- Notch signalling
three general rules for cell regeneration
- some tissues contain the same cells for the life of the organism, but the molecular components turn over
- typically cells with very specialized architecture - other tissues renew their cells rapidly
- typically cells exposed to harsh environments or activities - other tissues are between these extremes
specialized architecture of auditory hair cells in the organ of Corti
see lec 6 slide 3
- supporting cell
- outer hair cells
- tectorial membrane (mass of ECM)
- stereocilia
- inner hair cells
- basilar membrane
- nerve fibers
how the stereocilia work
1 hair cell : 4 stereocilia
- one stereocilia touches the membrane
- sound causes vibration causing the stereocilia to tilt
- tethers pull open ion channels on neighbouring stereocilia initiating a nerve impulse
pulse-chase experiment
- cells exposed to a radiolabeled leucine for a short time
- take up labeled AA and incorporate it into newly synthesized proteins for a short period of time
- leucine is detected but will gradually be lost (destroyed by pigment cells)
stem cell
- not terminally differentiated
- can divide without limit
- daughters can remain a stem cell or differentiate
stem cell mechanisms
- controlling fates of stem cell daughters
- dividing slowly for long term preservation
- supported by local environment (their niche)
controlling fates of stem cell daughters
- divisional asymmetry
- one daughter receives factors promoting stemness and the other promoting differentiation
- drawback: lost stem cells cannot be restored - environmental asymmetry
- environment promotes either stemness or differentiation
- stem cell numbers can be increased by having both daughters enter the environment promoting stemness
stem cells divide slowly for their LT preservation
protects the cell from
- mutations associated with cell division
- telomere depletion associated with cell division
large numbers of cells are needed to renew differentiated cell populations
- one cell kept safe
- one cell changes to a transit amplifying cell
stem cells are supported by a local environment
in skin cells, the basal lamina provides a niche for the stem cells
- after detaching from the basal lamina, the cells differentiate through a linear sequence of cell types
identifying blood stem cells and progeny
- cells separated by arbitrary differences (i.e. cell surface markers)
- the population that saves the mouse has stem cell activity
OR
- homogenize mouse bone marrow to release single cells
- expose to fluorescent antivodies recognizing specific cell surface molecules
- isolate using Fluorescence-Activated Cell Sorting
- isotonic fluid is made to be -ve
- negatively charged cell = fluorescence; positive = no fluorescence
how are blood stem cells maintained
through itneractions with stromal cells in the bone marrow
- stromal cell provides a niche for the blood stem cells
medical uses of stem cells
- blood stem cells to treat leukemia
IF IMMUNE REJECTION HAPPENS
- careful tissue matching and immunosuppressive drugs used
- patient’s own stem cells can be used after sorting if a cancer arises
can cells of a different tissue be used to make stem cells for treatment
- done in experiments, not for humans
- could avoid immune rejection but cancer development is a problem should cell differentiation go out of control
ways to avoid immune rejection of ES cells
- somatic cell nuclear transfer- use a nucleus from one of the patient’s own cells and transfer it into an unfertilized egg to develop an embryo to harvest ES cells
- treat some of the patient’s own cells with factors that generate ES cells –> oct3/4, Sox2, Myc and Klf4 (TFs) can convert differentiated cells into cells with ES characteristics
