Cellular & Molecular Mechanisms of Development II Flashcards
(35 cards)
What are growth factors?
smalld iffusible proteins that cells release into the extracellular environment
When growth factors are received by specific receptors on another cell, they can bring about a number of changes to that cell’s behavior, including:
- stimulation or inhibition of cell proliferation
- cell differentiation
- cell shape change
- stimulation or inhibition of cell migration
*all of these are important for regulating embryonic development
f
f
What is the general mode of action of growth factors?
cell (ex: notochord cell) secretes diffusible growth factor that can cross several membranes, the growth factor binds to corresponding receptor, which then changes intracellular and transcriptional properties of the cell
- final effect is change in protein synthesis in recipient cell. Leads to altered behavior
- only cells with the specific receptor can respond
Wnt growth factor family
- named after a Drosophila mutation called wingless and a human oncogene called int
- there are about 20 different Wnt proteins in mammals; all are expressed in the embryo
ex: fly with Wnt mutation won’t have wings!
The Transforming Growth Factor-Beta family
(involved in wound healing, Marfan’s syndrome)
- TGF-Beta1, Beta2, and Beta3
- Bone Morphogenetic proteins (BMPs) ??
- the receptors for these are threonine/serine kinases
i. e. they modify intracellular proteins by adding a phosphate to a serine or a threonine
Hedgehog growth factors
three hedgehog proteins called:
- sonic hedgehog
- indian hedgehog
- desert hedgehog
What are the other growth factor families?
- fibroblast growth factors (FGFs) - about 10 proteins
- platelet derived growth factors (PDGFs)
- epithelial growth factors (EGFs)
- vascular endothelial growth factors (VEGFs; very important in vascular formation)
- others
*all of these proteins bind to specific receptors
Even with this large number of growth factors, exactly the same proteins are used for regulation of numerous different developmental events.
for ex: BMP4 is active during blood formation, neural development, lung development, and bone growth
fix
Given the potency of growth factors, their expression is very closely regulated. Regulation occurs at the level of:
- transcription
- mRNA processing and stability
- translation
- post-translation activity
*when start releasing growth factors, cells also preparing to halt the process (cancer cells lose this ‘break’)
What are the inhibitors of BMP family proteins?
noggin and chordin
What are some examples of post-translational regulation? (inhibition)
***important I would assume
- BMP family proteins are bound by inhibitors called noggin and chordin
- Wnt family proteins are bound by inhibitors called Dickkopf and crescent
- Hedgehog is bound by an inhibitor called Hip (Hedgehog interacting protein)
*all of these inhibitors prevent the growth factors from binding to their receptors, thus blocking the signal
What are the inhibitors of Wnt
Dickkopf and crescent
What are the inhibitors of Hedgehog?
Hedgehog interacting protein (Hip)
Growth factor signaling is so fundamental to embryonic development, that it is very rare for embryos with growth factor defects to survive until birth. Approximately 50% of all pregnancies fail to reach term. What do you think many of these are possibly due to?
probable that defects in growth factor signaling account for many of these spontaneous terminations
A failure in holoprosencephaly causes what?
- brain may fail to form two lobes
- at its most extreme, holoprosencephaly may present as cyclopia
- cyclopia is a telltale sign of loss of Hedgehog signaling
What is holoprosencephaly?
- a specific growth factor
- results from reduction of sonic hedgehog signaling
- relates to a spectrum of defects primarily due to failure of formation of midline structures in neural tissues
What is induction?
At the large scale level, induction can be interpreted as one tissue (or region of the embryo) instructing another region.
ex:
- notochord inducing epidermis to form neural tissue
- notochord inducing scleretome
- endoderm induction of heart tissue
- heart induction of liver tissue
*all due to cell-signaling events mediated by growth factors
Induction is the result of what action?
result of action by signaling proteins (growth factors or inhibitors)
ex: Shh (Sonihc hedgehog) signaling from the notochord and the base of the neural tube induces nearby cells in somite to become sclerotome cells
Explain the induction of the heart.
- the heart forms from mesoderm where Wnt signaling is blocked
- this is achieved by a Wnt inhibitor called Crescent
- Crescent is expressed in the endoderm
(all of mesoderm is experiencing Wnt signaling; in region where Wnt signaling is switched off, heart can be formed)
*note: splanchnic mesoderm forms heart
Explain the induction of neural tissues
- in ectoderm (–> epidermis, skin), BMP (BMP-4) is present/expressed everywhere
- notochord secretes Noggin to inhibit BMP-4
- Neural tissue forms where BMP-4 signaling is absent
What are homeobox genes?
- important for many aspects of embryonic development
- all of these genes contain a conserved DNA sequence called the homeobox
- the homeobox encodes a DNA binding protein domain called the HOMEODOMAIN
- box is DNA sequence
- all homeodomain proteins are transcriptional regulators - either positive or negative
- there are about 150 homeobox genes in the human genome
- homeodomain is the protein sequence
What is the homeodomain?
- a DNA binding protein domain in the homeobox of homeobox genes
- all homeodomain proteins are transcriptional regulators - either positive or negative
about 150, all expressed in embryo
What are Hox genes?
- these are a subset of the homeobox genes that provide positional information in the embryo
- the Hox genes are arranged in clusters with up to nine genes in a row on the chromosome (mammals have 4 Hox clusters, flies have just 1; the order of the genes is the same in human and fly)
- these genes must therefore have arisen in an evolutionary ancestor of both mammals and insects
