Genetic Basis for Development

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GENETIC BASIS FOR
DEVELOPMENT
FROM CELL TO ORGANISM
Mitosis: makes multiple copies
Differentiation: specialization in
structure & function
Morphogenesis: organisms get their
shape
WHO SHOULD WE STUDY??
Organism must have short generations
& small genome
Try to create cell lineage (ancestry of
cell from the zygote stage) for study
NUCLEAR TRANSPLANTATION
Replace nucleus of unfertilized egg
cell or zygote with nucleus of
differential cell
Embryo & tadpole nuclei into egg
cells
Found that older donor nuclei
resulted in smaller % of development
NUCLEAR TRANSPLANTATION
Results:
Nuclei do change as they differentiate,
but the changes may be reversible
1997 “Hello Dolly”
Cloning of sheep – how?
NUCLEAR TRANSPLANTATION
Nucleus from udder cell into
unfertilized egg of another sheep
Dedifferentiation of nucleus
accomplished by putting cells in
nutrient-poor medium – cycle
stopped at G 1 – went to G 0
Fused with egg cell with nucleus
removed
Resulting embryo in surrogate
mother
NUCLEAR TRANSPLANTATION
Problem: many cloned mammals do not
develop properly
DNA is overly methylated
Interferes with gene expression
STEM CELLS
Unspecialized until they differentiate
Continually reproduce (replace
nonreproducing specialized cells as
needed)
Blood cells from bone marrow
Nerve cells in brain
Pluripotent: can give rise to multiple
cell types (like blood cells)
STEM CELLS
More in embryos than adults
Embryonic
stem cells
use
telomerase
to keep
telomeres
long to be
“immortal”
WHAT CAUSES THE BEGINNINGS OF
DIFFERENTIATION?
Cytoplasm of unfertilized egg cell
Has uneven distribution of mRNA,
proteins, organelles
After fertilization, mitosis in zygote
leads to cells exposed to different
environments
Influences course of early development
Regulates gene expression affecting
development fate of cells
Called cytoplasmic determinants
(MORE TO COME!!)
WHAT CAUSES THE BEGINNINGS OF
DIFFERENTIATION?
Environment around cell
Signal molecules (made by embryo’s
genes) send signal to target & alter
gene expression (induction)
Diffusion of
chemical signals
or surface cell-cell
interactions
PATTERN FORMATION
Development of spatial organization
where tissues & organs are in their
characteristic places
Begins as early embryo
Basic body plan established (head/tail
end)
PATTERN FORMATION
Positional formation: molecular cues
that control pattern formation
Location of cells relative to body axes &
other cells
How cell & offspring will respond to
future signals
PATTERN FORMATION:
DROSOPHILA
3 parts: head, abdomen, thorax
Bilateral symmetry
Anterior-posterior & dorsal-ventral axes
Cytoplasmic determinants position
axes
After fertilization, fine tuning triggers
characteristic structures based on
location
HOMEOTIC GENES
Master regulatory genes that set
anatomical identity
Encode transcription factors to build
parts
Homeobox: 180-nucleotide sequence in
homeotic genes found in many other
species
CELL COMMUNICATION
Induction brings about differentiation
through regulation of transcription
Ex) Vulval
development in
C. elegans
(nematode)
APOPTOSIS
Programmed cell death
Genes specific to cause this
Cell shrinks
Nuclei condense & break down
Neighbors engulf cell membrane
Believe mitochondria pay a role in
mammals
APOPTOSIS
Occurs in development – prevent
webbing of hands & feet; helps in
nervous system development
Could play a role in cancers &
degenerative nervous system disorders
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