Lecture 8: Molecular & Genetic Basis of Tooth Development

Question 1

what are neural crest cells?

Answer 1

stem cells formed at the BACK of the neural tube that begin migrating to the branchial arches laterally with the neural tube closes

Question 2

regarding teeth, what types of cells are created from NCCs?

Answer 2

• odontoblasts
• cementoblasts

*ameloblasts are from ectoderm epithelial cells

Question 3

how does the ectoderm affect the NCCs?

Answer 3

• regulates NCC cells during morphogenesis

- controls the position, size, and shape of organs

Question 4

how does the mesoderm affect the NCCs?

Answer 4

provides environment for NCC cells to populate

Question 5

how does the endoderm affect the NCCs?

Answer 5

develops pharyngeal pouch-generated organs (thyroid, parathyroid, and thymus)

Question 6

NCCs traveling to the first branchial arch come from where?

Answer 6

hindbrain rhmobomeres r1-2

Question 7

where do all 7 of the hindbrain rhomobomeres go?

Answer 7

• 1st arch: r1-2
• 2nd arch: r4
• 3rd arch: r6-7

Question 8

what is the correlation btw the branchiomotor nerves and the hindbrain rhobomeres?

Answer 8

• trigeminal nerve: r1-3
• facial nerve: r4-5
• glossopharyngeal nerve: r6-7

Question 9

if a hox gene is expressed, its protein product functions as a _____ which controls _____

Answer 9

• transcription factor
• gene expression

*specific NCC streams = specific hox gene profile

Question 10

which branchial arch is considered hox free?

Answer 10

1

• carry the genes but do not express them
• r4 in the 2nd arch is where hox genes first are expressed

Question 11

NCCs involved in ______ do NOT express hox genes

Answer 11

tooth development

Question 12

within the first branchial arch, specific ____ gene codes are expressed to produce differences between the maxilla and mandible

Answer 12

Dlx gene (transcription factor)

• Dlx 1&2 for maxillary molars
• Dlx 5&6 for mandibular molars

Question 13

all tooth structures, except for ___, are directly contributed by cranial neural crest cells that migrated to the 1rst branchial arch

Answer 13

enamel

*cranial neural crest cells directly contribute to the development of dentin, cementum, pulp and PDL BUT NOT enamel

Question 14

what are the 4 major signaling pathways of the ectoderm derived epithelium?

Answer 14

• BMP (none morphogenic protein)
• FGF (fibroblast growth factor)
• Wnt (wingless & int)
• SHH (sonic hedgehog)
• all four bind to cell membrane receptors and impact gene regulation
• important for development of hair, nails, and glands

Question 15

appear by the END of bud stage and are essential for the bud-to-cap stage transition, where without it, tooth development will be arrested

Answer 15

primary enamel knot

Question 16

appear at locations of future molar cusps at the bell stage an determine the number and locations of molar cusps

Answer 16

secondary enamel knot

Question 17

what are the differential expressions of signaling molecules in the enamel knots that determine cusp patterns?

Answer 17

• FGF (cusp activator)

- BMPs and SHH (inhibitor to regulate intercusp distance)

Question 18

what are the important molecules produced by the MESENCHYMAL cells for tooth development?

Answer 18

• signalling molecules: BMP, FGF, Wnt, and their inhibitors

- transcription factors: Msx1/2, Dlx1/2, Pax9, Gli2/3, Runx2, Barx1

Question 19

at the cell and molecular level, the development of a tooth crown ken be divided into three major stages

Answer 19

1. initiation
2. morphogenesis
3. differentiation and mineralization

Question 20

concerning dental innervation, pioneer trigeminal axons penetrate into the dental pulp when?

Answer 20

after the start of enamel formation

*enamel needs to be there to protect it

Question 21

concerning dental innervation, what is Sema3A responsible for?

Answer 21

serves as a chemorepellent for the axons, thus controlling the timing and patterning of tooth innervation

Question 22

although enamel is not present in the final root, what is required for root development?

Answer 22

induction from the epithelium (HERS)

*HERS induces the dental papilla to differentiate into apical odontoblasts

Question 23

what is required for ROOT dentin formation but NOT for CROWN dentin formation?

Answer 23

nuclear factor Ic (Nfic)

Question 24

when does cementum formation begin?

Answer 24

when HERS and dental follicle cells are in close proximity

*both epithelial cells (HERS) and mesenchymal cells (dental follicle) participate, but contributions remain unclear

Question 25

concerning the interaction between epithelium and mesenchyme during ROOT development, what are the currently known molecules involved?

Answer 25

HERS: TGF-b, Nfic, insulin like growth factors, Wnts, FGF
Mesenchyme: BMP, FGF

*compared to the molecules involved in CROWN development, most molecules for ROOT development are different

Question 26

what are the contributions of HERS to root development?

Answer 26

• HERS do not respond to signals from the mesenchyme and DO NOT differentiate into ameloblasts
• induce differentiation of ODONTOBLASTS and CEMENTOBLASTS
• determines the number of roots

Question 27

what can possibly happen to the HERS after root development ?

Answer 27

• become epithelial rest of malassez
• apoptosis
• incorporated into the cementum front
• epithelial-mesenchymal transformation
• migrate to the PDL
• differentiate into cementoblasts

Question 28

what gene mutations are currently known to be related to missing teeth?

Answer 28

• Msx1 : transcription factor
• Pax9 : transcription factor
• Axin2 : signaling molecule, Wnt pathway
• EDA : signaling molecule, TNF pathway
• p63 : transcription factor, BMP, FGF, SHH pathways

Question 29

what gene mutations are currently known to be related to supernumerary teeth?

Answer 29

• Runx2 : transcription factor

- Apc : signaling molecule, Wnt pathway