molecular/genetic tooth development Flashcards
when do CNCCs start migrating
when the neural tube closes
where do the CNCCs migrate to
they take defined paths to the branchial arches
what week are branchial arches formed
week 4
teeth develop from which branchial arch
BA 1
development of the BA structures at the right location and time depend on…
precise tissue-tissue interactions
what is the tissue interactions b/w the NCC and the ectoderm
ectoderm regulates NCC cells during morphogenesis and controls the position, size and shape of the organs
what is the tissue interactions b/w the NCC and the mesoderm
mesoderm provides environment for the NCC to populate
what is the tissue interactions b/w the NCC and the endoderm
endoderm develops pharyngeal pouch generated organs (thyroid, parathyroid, and thymus)
hindbrain consists of
7 segments called rhombomeres. the NCCs here migrate in 3 streams (r1-2/r4/r6-7)
1st BA’s NCCs come from
r1-2
2nd BA’s NCCs come from
r4
3rd BA’s NCCs come from
r6-7
the branchiomotor nerves (nerves that supply the BA structures) exit the hindbrain only from
even numbered segments/rhombomeres to innervate their peripheral structures
trigeminal nerve supplies
r1-3, 1st branchial arch structures INCLUDING THE TEETH
facial nerve supplies
r4-5
glossopharyngeal supplies
r6-7
NCCs in each migratory stream express
specific Hox gene codes. So specific NCC streams have a specific Hox gene profile
Hox genes defined
a group of homeobox genes which possess a unique DNA sequence, which encodes a conservative protein segmen/homeodomain (aka a family of genes that have a specific DNA sequence that encodes for a particular protein)
if a Hox gene is expressed, its protein fns as a
transcription factor which controls other gene expression
NCCs that migrate to BA 1 (r1-2) are
Hox free. They carry the genes, but don’t express them
NCCs involved in tooth development
do NOT express Hox genes
D1x gene
homeobox gene that is expressed as transcription factors. (related to the drosophila distal-less gene). 7 members of the D1x family (1-7).
within the first BA, what is the job of the D1x gene
when expressed, it produces differences b/w the maxilla and the mandible (both derived from BA 1)
D1x1/2 is required for the development of
proximal portion of the 1st branchial arch..which is the maxillary process
D1x5/6 is required for the development of
distal portion of the 1st branchial arch..which is the mandibular process
D1x5/6 double mutants develop…
lower jaws that look just like the upper jaw
are Hox genes expressed in NCCs that travel to the 2nd BA
yes
what allows tooth development to get from stage to stage
it is precisely arranged and regulated by cell and molecular interactions
all tooth structures (except for enamel) are directly contibuted by
CNCCs that migrated to the 1st BA. CNCCs contribute to the development of the dentin, cementum and the PDL (not enamel)
what are the 4 major signaling pathways for ectoderm derived epithelium
- BMP
- FGF
- Wnt
- SHH
they are also important for the development of other ectodermal organs (hair, nails, glands)
what is similar b/w all 4 signaling pathways
all of the molecules bind to cell membrane receptors and are able to regulate gene expression via intracellular pathways.
what is an enamel knot
epithelial aggregates that fn as signal centers for morphogenesis and odontoblast differentiation
primary enamel knot appears
at the end of the bud stage
what is the job of the primary enamel knot
strongly stimulates the proliferation of adj cells. essential for bud-to-cap stage transition. (would be arrested w/o it).
how does the primary enamel knot disappear
cell apoptosis
the secondary enamel knot appears
at the locations of future molar cusps at the BELL stage
what is the job of the secondary enamel knot
stimulates the terminal differentiation of odontoblasts at the end of the bud stage, this always occurs first at the location of the future cusp tips. also determines the number and location of the molar cusps. (not present in incisors)
what determines the cusp patterns
differential expression of signaling molecules in the EK
FGF fns as a
cusp activator
BMPs fn as a
inhibitor to regulate the formation of inter-cusp distance
at the cell/molecular level, development of the tooth crown can be divided into 3 major stages
- initiation
- morphogenesis
- differentiation and mineralization
what is the difference b/w the determination of incisors vs molars
though that different molecular interactions are present at the anterior compared to the posterior which controls what develops where
innervation of the teeth is from what CN
trigeminal axons
when do nerves enter the dental pulp
after the start of enamel formation/ bell stage
what expresses Sema3a
epithelium
what is the fn of Sema 3a
chemorepellent for axons. so it controls the timing and patterning of tooth innervation.
is induction from the epithelium required for root development
yes
what is secreted by HERS to stimulate dental papilla cells to differentiate into apical odontoblasts
lamini-5 and TGF-beta
what is nuclear factor Ic (NFIC) for
root dentin formation…not crown dentin. without NFIC, odontoblasts cannot form even when HERS is normal
when does cementum formation start
when HERS and the dental follicle are in close proximity. Both HERS/epithelial and mesenchymal/dental follicle cells participate
contributions of HERs to root development
- don’t respond to mesenchyme signals and do not differentiate into ameloblasts
- induce differentitation of odontoblasts
- induce the differentiation/transdifferentiate into cementoblasts
- determine the number of root canals
fates of HERS
- epithelial rests of malassez
- apoptosis
- incorporated into the cementum front
- epithelial-mesenchymal transformation
- migration into PDL
- differentiation into cementoblasts
are molecules involved for root development the same as those involved in crown development
no. HERS (FGF, Wnt, TGFbeta, NFIC, IGF). Mesenchyme (BMP, FGF)
ectodermal displasia syndrome
2 or more ectodermal structures are affected
what is the mutation for ectodermal displasia syndrome
t.f p63. normally required for the normal fn of FGF, BMP, and SHH (which are all required for epithelial-mesenchyme interactions) so when altered, tooth development is not normal
Msx1 mutation causes
lack both maxillary premolars and mandibular 2nd premolars.
how is Msx1 mutated
G–>C transversion (arg–>pro) that causes an Msx1 gene mutation
what does Msx1 normally do
it is a t.f that is expressed in the mesenchyme and is involved in tooth development. mutation is at the homeodomain region affects the normal t.f protein fn.
Pax 9 mutation causes
no molar development
how is Pax 9 mutated
guanine insertion that causes a frame shift of the Pax 9 gene
what does Pax9 normally do
it is a t.f expressed in the mesenchyme for tooth development. mutation is at its DNA binding domain which affects it as a t.f.
Axin2 mutation causes
more than 8 permanent teeth underdeveloped. patients may be susceptible to colorectal polyps and cancer
how is Axin2 mutated
missense C–>T or G insertion causing a premature stop codon in the Axin2 gene
what does Axin2 normally do
it is expressed extensively in the mesenchyme and loss of its fn disrupts Wnt signalling for tooth development. it is NOT a t.f
EDA mutation causes
multiple missing anterior teeth. x-linked dominant
how is EDA mutated
have missense C–>G mutation that results in a Q to E substitution in EDA
what does EDA normally do
it is a transmembrane signalling molecule that belongs to the TNF pathway. it is NOT a t.f.
supernumerary teeth related to what 2 systemic conditions
- cleidocranial dysplasia
2. gardner’s syndrom
what causes cleidocranial dysplasia
Runx2 mutations
what is Runx2
t.f expressed by the mesenchyme that is essential for tooth development. positive regulator for primary teeth but negative regulator for secondary teeth
gardner’s syndrome is causes by
APC mutation. mediate by the beta catenin pathway/wnt pathway
