Lecture 8: Molecular & Genetic Basis of Tooth Development Flashcards
what are neural crest cells?
stem cells formed at the BACK of the neural tube that begin migrating to the branchial arches laterally with the neural tube closes
regarding teeth, what types of cells are created from NCCs?
- odontoblasts
- cementoblasts
*ameloblasts are from ectoderm epithelial cells
how does the ectoderm affect the NCCs?
- regulates NCC cells during morphogenesis
- controls the position, size, and shape of organs
how does the mesoderm affect the NCCs?
provides environment for NCC cells to populate
how does the endoderm affect the NCCs?
develops pharyngeal pouch-generated organs (thyroid, parathyroid, and thymus)
NCCs traveling to the first branchial arch come from where?
hindbrain rhmobomeres r1-2
where do all 7 of the hindbrain rhomobomeres go?
- 1st arch: r1-2
- 2nd arch: r4
- 3rd arch: r6-7
what is the correlation btw the branchiomotor nerves and the hindbrain rhobomeres?
- trigeminal nerve: r1-3
- facial nerve: r4-5
- glossopharyngeal nerve: r6-7
if a hox gene is expressed, its protein product functions as a _____ which controls _____
- transcription factor
- gene expression
*specific NCC streams = specific hox gene profile
which branchial arch is considered hox free?
1
- carry the genes but do not express them
- r4 in the 2nd arch is where hox genes first are expressed
NCCs involved in ______ do NOT express hox genes
tooth development
within the first branchial arch, specific ____ gene codes are expressed to produce differences between the maxilla and mandible
Dlx gene (transcription factor)
- Dlx 1&2 for maxillary molars
- Dlx 5&6 for mandibular molars
all tooth structures, except for ___, are directly contributed by cranial neural crest cells that migrated to the 1rst branchial arch
enamel
*cranial neural crest cells directly contribute to the development of dentin, cementum, pulp and PDL BUT NOT enamel
what are the 4 major signaling pathways of the ectoderm derived epithelium?
- 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
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
primary enamel knot
appear at locations of future molar cusps at the bell stage an determine the number and locations of molar cusps
secondary enamel knot
what are the differential expressions of signaling molecules in the enamel knots that determine cusp patterns?
- FGF (cusp activator)
- BMPs and SHH (inhibitor to regulate intercusp distance)
what are the important molecules produced by the MESENCHYMAL cells for tooth development?
- signalling molecules: BMP, FGF, Wnt, and their inhibitors
- transcription factors: Msx1/2, Dlx1/2, Pax9, Gli2/3, Runx2, Barx1
at the cell and molecular level, the development of a tooth crown ken be divided into three major stages
- initiation
- morphogenesis
- differentiation and mineralization
concerning dental innervation, pioneer trigeminal axons penetrate into the dental pulp when?
after the start of enamel formation
*enamel needs to be there to protect it
concerning dental innervation, what is Sema3A responsible for?
serves as a chemorepellent for the axons, thus controlling the timing and patterning of tooth innervation
although enamel is not present in the final root, what is required for root development?
induction from the epithelium (HERS)
*HERS induces the dental papilla to differentiate into apical odontoblasts
what is required for ROOT dentin formation but NOT for CROWN dentin formation?
nuclear factor Ic (Nfic)
when does cementum formation begin?
when HERS and dental follicle cells are in close proximity
*both epithelial cells (HERS) and mesenchymal cells (dental follicle) participate, but contributions remain unclear
concerning the interaction between epithelium and mesenchyme during ROOT development, what are the currently known molecules involved?
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
what are the contributions of HERS to root development?
- 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
what can possibly happen to the HERS after root development ?
- become epithelial rest of malassez
- apoptosis
- incorporated into the cementum front
- epithelial-mesenchymal transformation
- migrate to the PDL
- differentiate into cementoblasts
what gene mutations are currently known to be related to missing teeth?
- Msx1 : transcription factor
- Pax9 : transcription factor
- Axin2 : signaling molecule, Wnt pathway
- EDA : signaling molecule, TNF pathway
- p63 : transcription factor, BMP, FGF, SHH pathways
what gene mutations are currently known to be related to supernumerary teeth?
- Runx2 : transcription factor
- Apc : signaling molecule, Wnt pathway
