Signalling Pathways

Question 1

Which tissue initiates tooth development?

Answer 1

Oral ectoderm

Question 2

Where is Pax9 expressed?

Answer 2

Oral mesenchyme of tooth germs

Question 3

What three ways can cells signal to each other?

Answer 3

Direct contact (proteins in cell membranes)

Gap junctions (channels)

Diffusion (of secreted substances)

Question 4

What is the main method of communication in tooth development?

Answer 4

Diffusion

Question 5

Give examples of (families of) growth factors. (4)

Answer 5

Hedgehogs

Wnts

FGF

BMP

Question 6

What are the three steps in the conversion of a signal into a response in a cell?

Answer 6

1. Reception
2. Transduction
3. Response

Question 7

What is the first active gene in the oral ectoderm?

Answer 7

Pitx2

Question 8

What growth factors are expressed in the oral epithelium? (4)

Answer 8

BMP

FGF

SHH

WNT

Question 9

What growth factors are expressed in the oral mesenchyme? (4)

Answer 9

BMP

WNT

FGF

Activin

Question 10

Which tissue determines the tooth type?

Answer 10

Mesenchyme

Question 11

What patterns the dentition?

Answer 11

Homeobox transcription factors expressed in the mesenchyme

Question 12

How does FGF from the oral epithelium affect dentition patterning?

Answer 12

Molars formed

Question 13

How does BMP from the oral epithelium affect dentition patterning?

Answer 13

Incisors formed

Question 14

Where is FGF expressed in the oral epithelium during dentition patterning?

Answer 14

Proximally/molar region

Question 15

Where is BMP expressed in the oral epithelium during dentition patterning?

Answer 15

Distally/incisor region

Question 16

Which homeobox genes lead to the formation of molars?

Answer 16

Dlx1/2

Barx1

Question 17

Which homeobox genes lead to the formation of incisors?

Answer 17

Msx1/2

Question 18

What does overlapping of homeobox gene expression lead to?

Answer 18

Formation of intermediate teeth (premolars)

Question 19

What suppresses Barx1 expression to prevent molar formation and where is it expressed?

Answer 19

BMP4

Incisor mesenchyme

Question 20

What substance inhibits BMP4?

Answer 20

Noggin

Question 21

Describe the SHH signalling. (4)

Answer 21

1. SHH binds PTCH1 receptor to release inhibition of SMO receptor expression
2. SMO expression induces formation of Gli-activator molecules (transcription factors)
3. Gli-activator molecules enter nucleus and activate SHH target genes (Gli1, Ptc1)
4. PTCH1 also activated to amplify signalling/positive feedback

Question 22

Where is SHH strongly expressed?

Answer 22

DENTAL oral epithelium

Question 23

What will lack of SHH signalling cause?

Answer 23

Arrest of tooth development at initiation/no bud stage

Question 24

The interaction between which two growth factors controls the dental oral epithelium boundaries?

Answer 24

SHH

WNT-7b

Question 25

Where is WNT-7b expressed?

Answer 25

Where gaps will form (non-dental oral epithelium)

Question 26

How do WNT-7b and SHH interact?

Answer 26

WNT-7b suppresses SHH signalling to prevent tooth formation

Question 27

Describe BMP signalling. (3)

Answer 27

1. BMP binds receptor which forms a complex containing R-I and R-II 2. Complex is phosphorylated and then phosphorylates R-smad and co-smad proteins 3. R-smad and co-smad enter nucleus and regulate gene expression

Question 28

Describe BMP4 secretion in PEK formation.

Answer 28

Secreted from epithelium to cause Msx1 expression in mesenchyme Msx1 and Pax9 cause BMP4 secretion from mesenchyme to induce PEK formation

Question 29

What would happen to the PEK if Msx1 was knocked out and why?

Answer 29

No BMP4 released from mesenchyme back to epithelium so no PEK

Question 30

Describe the expression of genes/factors during the bud stage.

Answer 30

Msx1 and Pax9 highly expressed in mesenchyme BMP4 mainly expressed in mesenchyme (little in bud) SHH only in PEK

Question 31

How does the repression of Msx1 or Pax9 affect humans?

Answer 31

SOME tooth development is arrested (hypodontia)