Lecture 3 - Signaling and Genetics of Craniofacial Development Flashcards

1
Q

Importance of BMP 2 and BMP 7

A

They are FDA approved growth factors that can be given to bone defets. Will promote osteoblast differentiation
And Accelerate bone healing

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2
Q

TGF-Beta superfamily Consists of

A
Growth factors!!
Three subfamilies
BMP
TGF-beta 
and Activin 
signal transduction path is similar
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3
Q

Potency of BMP?

A

Very potent so only seen in very small amount

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4
Q

What two things are required for Signal Transduction, and what is typically seen as the order

A

Requires - Protein -protein interaction
requires - post translational modification
Typically needs growth factor, receptor, signal transducer, transcription factor

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5
Q

Growth Factor Qualities

A

Usually bind with high specificity to membrane proteins

Binding results in a complicated cascade of secondary messengers that express transcription of certain genes

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6
Q

Signal Transducers

A

Molecules utilized for intracellular signaling from membrane to nucleus. Transmit information
They are information carriers

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7
Q

Smad in TGF/BMP signaling

A

signal binds to tyrosine kinase, dimerize, cross phosphorylate, and goes to phosphorylate the smad complex. Smad goes to nucleus for targeting gene expression

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8
Q
Other Examples of Signal Transducers in these paths
MAP Kinase Signaling
JAK/STAT signaling 
NF-kB signaling 
and Wnt Signaling
A

MAPK
JAK/STAT
IKK
GSK and Beta Catenin

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9
Q

Transcription Factors

A

molecules proteins which bind to DNA sequence to control transcription. Recruit RNA polym
activate or repress

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10
Q

Examples of TFs for the following paths

A

Smad - in TGF/BMP path
Jun or fos in MAP kinase signaling
NF-kb in NF-kB path
B catenin in wnt signaling

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11
Q

How Growth Factors are Controlled (after secretion from cell)

A

1) prodomain - attaching full protein to a inactive molcule (must be removed)
or
2) ECM binding protein sticks the growth factor bindding at the membrane
3) ECM antagonist - can cluster around it and inactivate it
Or
4) stored within the ECM

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12
Q

Growth Factor Pathway for TGF-B signaling

A

propeptide - makes a small latent complex (SLC)
latent TGF-Beta binding protein (LTBP) which makes a large latent complex with SLC becomes LLC
so the slc get attached and thus creates a large latent complex that must dissociate or hae exposure of binding region
Fibrillin, collagem are very important for GF control also

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13
Q

Where diseases affect craniofacial development
Marfan
LDS (loeys Dietz Syndrome)
FOP (fibrodysplasia ossificans progressive )

A

1) Fibrillin (ECM protein)
2) TGF-Beta Receptor, also we see a bifid uvula as a different thing
3) - BMP Receptor (subfam of TGF)

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