Lecture 15: How Cells Become Different Flashcards
Understand that gene expression can be regulated at many different levels • Understand the concept of promoter • Understand that transcriptional regulators are DNA binding proteins that can act as activators or repressors • Understand how the Lac operon is regulated in bacteria • Appreciate the complexity of eukaryotic transcriptional regulation • Understand the definition of enhancers and their roles in transcriptional regulation
zygote -> cleavage (morula) -> blastula -> gastrula
intially totipotent -> later become less potent, more specified
how do cells become different
step-wise restriction of “cell fate potential”
-cell intrinsic (cell autonomous) - making cells different, asymmetric cell divsion
-cell extrinsic (non-cell autonomous) - cell-cell communuication w/ outside env. (signals)
what makes cells different
differential gene expression
terminally differentiated: potential is reached, cannot become anything else
cell fate
describes what cells will normally develop into
differentiated cell:
cell thst has become specialized (e.g. liver)
usually refers to terminal state of a cell but can also refer to intermediate states (mesoderm, endoderm, etc.)
commitment
cells may have become committed to a particular fate even though they may not look differentiated
the process of commitment can be divided into two phases:
specification: commitment to a particular fate, but in a lanile or reversible manner
determination: irreversible commitment to a particular fate
test of specification (isolation experiment)
put the cell or tissue in isolation in a neutral environment (e.g. tissue culture) what does the cell become?
- if it expresses a different fate than it would normally, it was NOT specified and NOT determined
- if it expresses its normal fate, it is specified but may or may not be determined.
must do peturbation to know if differentiated
in vitro (in a dish) test for determination
put the cell or tissue in a new environment. what does the cell become?
- if it still expresses its normal fate, then it is determined
- if not, then it is not determined
in vivo test for determination
cells are DETERMINED if transplantation from their normal position to a new position in the embryo does not change their normal fate
ask tutor for help
commitment to a particular fate is progressive
each step is irreversible -> cells have memory
cell fate becomes increasingly restricted during development
is the genome changing during development?
test: nuclear transplantation
first animal cloning experiment
Gurdon (!962) showed that the nucleus from fully differentiated tadpole skin cell can direct normal frog development
clone frogs look like donor frogs
nucleus contains all info needed to develop
differential gene expression theory
- the genome is contant in all somatic cells
- only a small proprotion of the gneome in any cell type is expressed
- different cell types express different groups of genes that confer unique cellular characteristics
- unused genes that are not transcribed are not mutated or destroyed; they retain potential to be expressed (skin cells can be reactivated/reprogrammed)
differential gene expression makes cells different
ask tutor to explain
cell autonomous (ASYMMETRIC cell divsion)
cell intrinsic mechanism
sister cells are born different
asymmetric cell divsion
1 cell -> 2 different cells
non-cell autonomous
cell extrinsic mechanism
involves “cell signaling”
sister cells become different as a result of influences acting on them after their birth
inductive signaling; lateral inhibition
cell signaling is …
a major cell EXTRINSIC mechanism of cell diversification and organismal development
extracellular signaling molecule examples
proteins, peptides, amino acids, nucleotides, steroids, fatty acid derivatives, gases
signaling molecule could be: part of the extracellular space, attached to another cell, flowing through the circulatory system
cell signaling diagram
intracellular: relay, amplify, integrate, distribute
effector may alter: gene expression, metabolism, cytoskeleton
response: cell division, growth, survival, migration, secretion, contraction, differentiation
ask tutor
inductive signaling
some inductive signals function in an all-or-none manner
some inductive signals function in a concentration-dependent manner- morphogens
signaling molecules can function as morphogens (what are they?)
a morphogen is…
a diffusable molecule secreted from a source (Signaling cell or cells)
forms a graded distribution (concnetration gradient: higher near the ource and lower farther away)
produces specific cellular responses depending on its local concentration
provides a mechanism to specify fates in a reproducible pattern
example of a morphogen gradient
inappropriate expression of Shh or Shh signaling causes extra digit form
ask tutor
lateral inhibition
cells born as equivalent cells can adopt different fates in the absence of tissue asymmetries ( due to cell-cell communication)
both cells produce the same amount of X, and inhibit the production of X in their neighbor equally
a transient increase in X produced by cell 1 causes a stronger inhibition of X production by cell 2
a decrease in X produced by cell 2, allows cell 1 to make more X
how does lateral inhibtion work?
group of equivalent cells, cells compete by inhibiting neighbors, some cells predominate
lateral inhibtion works between two neighboring cells that are directly adjacent to each other
in sum - how do cels become different?
cell-cell communication in animal development is mediated by only a small number of conserved cell-cell signaling pathways, including
transforming growth factor-B (TGFB)
Wnt
Hedgehog (Hh)
Notch
Receptor tyrosine kinase (RTKs)
yet, there is enormous cell diversity in animals
the same inductive signal can…
generate different responses
initally identical but receive diff. signals due to location
sequential induction
initially 2 groups of cells that can generate a lot of cell diversity from signals
