hedgehog and wnt Flashcards
what do the 3 different hedgehogs do?
Sonic Hh- development of the CNS
Indian Hh- cartilage and bone
Desert Hh- development of peripheral NS
in the absense of Hedgehog signalling, what is the different components of the Hh pathway doing?
in the absense of the Hh ligand, Ptc is actively blocking Smo and and preventing it from doing its job so no transcription is happening.
what is physically preventing regulation from happening
well Gli wants to be in the nucleus transcribing shit but it cant cuz it keeps being phosphorylated and destroyed. it need a knight in shining armor
how do the transcription regulators get turned on?
when hedgehog ligand is around, it binds to Ptch, (distracts Ptc) which releases Smo, Smo goes into the cell and shuts down the mutherfucker phosphorylating Gli. Now Gli can roam free into the nucleus and do its thing transcribing shit
what happens if you phosphorylate Gli and who does it?
Gli is usually being phosphorylated and getting degraded, if Smo gets loose from Ptch and gets in the cell, it can phosphorylate the Gli phosphorylater and free Gli and let them do their jobs
where in the cell is the SHh signal recieved in vertebrates?
the primary cilium because vertebrates have cilium and invertebrates dont. Primary cilium are non motile cilia some in ear
a ciliopathy can have an
underlying hedgehog defect as well because those are the cells this pathway happens in
how are Shh’s used as morphogens?
Shh can be moved from one side of an embryo to another and it will create an identical body part on that side
what does a reduced Dentate Gyrus when Smo is being inhibited mean?
it means you need the Shh pathway for proper development of those cells
If a mutation happens in the Hh pathway in addition to reduced signalling in the pathway, what else can you have?
increased Gli repression activity (hella phosphorylation)
what is holoprosencephaly
developmental disorder characterized by incomplete midline formation (fused 1 brain). caused from mutation in SHh pathway. you can get several levels
even in the presence of Hh ligands, what is another means by which you can shut down the Hh pathway?
you can shut down the Hh pathway with cyclopamine which is a drug that inhibits Smo. If you have no Smo, you have no knight in shining armor thus Gli cant do shiiiiiiit.
what is the structure of smoothened (Smo) and how can it be used as a basis for cancer treatment
its a 7-alpha- helix G protein. Because its this type of protein and we know cyclopamin can block it, maybe we can use cyclopamine to block 7-a-helix protiens in other cells
how is the Hh ligand processed/ made. how can mutations affect this
Hh protein is made as a longer precurser. it cleaves itself and then cholesterol is covalently added to the C terminus of the N half. once the cholesterol is added, it is now good to go. there are mutations that prevent this from happening and this causes holoprosecephaly. even a depletion in cholesterol can cause this
what happens to the Hh pathway when i lower cholesterol
you can have holprosecephaly because you need cholesterol to process Hh ligands
without signalling what is TCF doing?
actively blocking transcription in the nucleus but as soon as B-catenin is activated, it goes in the nucelous and turns TCF into an active trancriber of genes (turns a hoe into a housewife)
what happens when APC gets mutated?
APC is not around to shut down B-catenin so you get overactive Wnt pathway which usually leads to cancer
