BIOL 303 Study Questions Set 3
Induction: one group of cells influences another group of cells to take on a
different fate. Frequently between epithelium and mesenchyme cells (organs)
Paracrine factor: signal produced by inducer (soluble protein, peptides or
Competence: ability to respond to a specific inductive signal. Needs to have an
Signal transduction: a signaling molecule activates a specific receptor protein on
cell membrane, then a second messenger transmits signal into the cell.
Differentiation: The process by which an unspecialized cell becomes specialized
into one of the many cell types that make up the body.
Commitment: Describes a state in which a cell’s developmental fate has become
restricted even though it is not yet displaying overt changes in cellular
biochemistry and function. The cell may not look different – but it is now more
limited as to what it will become.
What is the difference between endocrine signaling and paracrine signaling?
Endocrine signaling: hormones in circulatory system that act along a great
Paracrine signaling: localized production of paracrine factors (soluble proteins,
peptides or glycoproteins) secreted into extracellular space.
What is the difference between instructive and permissive induction?
Instructive: a signal from the inducing cell is necessary for initiating new gene
expression in the responding cell.
Permissive: the responding tissue has already been specified and only needs an
environment that allows for the expression of these traits (ex. Requires a
What is an example of an inductive interaction that shows regional specificity and
what is meant by genetic specificity?
Regional specificity: process by which different areas are identified in the
development of the early embryo. The process by which the cells become
specified differs between organisms.When cells from different regions of the
dermis (mesenchyme) are recombined with the epidermis (epithelium), the type of cutaneous structure made by the epidermal epithelium is determined by the
original source of the mesenchyme.
Genetic specificity: the mesenchyme instructs the epithelium as to what genes to
activate, but that set of genes must be present in the genome.
What is the difference between paracrine, juxtacrine and autocrine interactions?
Paracrine: proteins synthesized by one cell can diffuse over small distance to
induce changes in neighboring cells.
Juxtacrine: cell membrane proteins on one cell surface interact with receptor
proteins on adjacent cell surfaces.
Autocrine: the same cells that secrete paracrine factors also respond to them
In what general way are signals associated with paracrine factors transduced into the
Receptors are transmembrane proteins.
When ligand binds they undergo a conformational change (tyrosine kinase).
Ligand binding can cause dimerization, autophosphorylation, and conformational
What are the four main families of paracrine factors?
Fibroblast growth factor (FGF)
Transforming growth factor (TGF-Beta)
Looking at the regulation of the HEDGEHOG signaling pathway, what would be the
overall outcome on the transcriptional response (up/down) of HEDGEHOG responsive
HEDGEHOG: protein; transmits information to embryonic cells required for proper
development; key regulator of development in all bilaterians; gives rise to
segmented body pattern
SMOOTHENED: protein, bound to patched
CUBITUS INTERUPTUS: protein that depends on smoothened
Hedgehog Patched Smoothened Cubitus Interuptus Transcription
Hedgehog paracrine factor is processed before being secreted and must be
activated by binding to a molecule of cholesterol.
o HEDGEHOG binds PATCHED and the conformation of PATCHED changes
o This relieves the inhibition of SMOOTHENED
o Activation of SMOOTHENED releases CUBITUS INTERUPTUS and CI is
o Free CI protein enters nucleus o Nuclear CI binds Cubitis Binding Protein and activates target genes
a) The function of PATCHED is eliminated by a mutation
If PATCHED receptor cannot bind HEDGEHOG protein, then PATCHED represses
SMOOTHENED. Without SMOOTHENED activity the CUBITUS INTERUPTUS
protein remains bound to microtubules COS2 and FUSED, where it is cleaved by
PKA and SLIMB. One of the cleaved products is a nuclear transcription repressor
and no transcription of HEDGEHOG responsive genes takes place.
b) Function of CUBITUS INTERUPTUS is reduced by mutation
CUBITUS INTERUPTUS cannot be freed form microtubules and will not be able to
enter nucleus and bind to CBP protein that will activate HEDGEHOG genes.
c) Post-translational modification of HEDGEHOG is prevented
The pathway will not go forth. HEDGEHOG requires to be bound to a molecule of
cholesterol to be activated.
d) Cells are treated with a drug that increases the activity of SMOOTHENED.
More CI will be cleaved and free to enter nucleus to bind to CBP and create
In general, Notch signaling is different from other signaling pathways because it is very
sensitive to the total amount of Notch receptor (called dosage sensitivity). Looking at
the mechanism of Notch signal transduction, can you suggest a reason why this would
Notch is a receptor that binds Delta. Notch protein undergoes a conformational
change upon binding. Notch becomes a substrate for presenilin-1 protein. The
cleaved portion of Notch is localized to the nucleus and activates transcription
Notch spans the cell membrane. Receptor is triggered via direct-cell contact,
where the transmembrane protein of the other cell binds to the Notch receptor.
Notch: example of juxtacrine interaction (cell membrane proteins on one cell
surface interact with receptor proteins on adjacent cell surfaces). No diffusion of
inducer because the ligand and receptor are both transmembrane proteins.
There is no amplification step during signal transduction, unlike other pathways.
Each activated Notch receptor molecule is consumed during signaling, yielding
one Notch intracellular domain (from receptor, is cleaved upon binding a ligand).
This suggests there is a stoichiometric relationship between input and output (ie
one in, one out) and signal strength is important for generating the appropriate
cellular response. Both haploinefficiency (only one functional copy of the gene
does not produce enough gene product to bring about a wild-type phenotype)
and extra copies can produce this effect.