Odontogenesis: cellular and Molecular Flashcards
number of chromosomes in people
22 pairs of autosomes
1 pair of sex chromosomes
Germ cells
Gametes (spermatozoa and ova)
what do gametes hold
1 chromosome from each pair of chromosomes
DNA that encodes a protein product
Gene
Genomic DNA is converted to mRNA in the nucleus
Transcription
mRNS serves as a template for making a protein out of amino acids in the cytoplasm
Translation
Different versions of the same gene
Allele
Genetic makeup of an individuals (what alleles do they carry)
Genotype
Observable characteristics from the genotype and envrionment
pHenotype
A change in nucleotide sequence of a gene
Mutuations
Mutation in germline is what
Heritable and passed to offspring
A hereditary disease that affects bones and teeth
Osteogenesis imperfecta (OI)
what is mutatated in Osteogenesis Impoerfectta
COL1A1 (type I collagen)
what type of mutation is Osteogenesis imperfecta
Autosomal dominant
what is the result of an autosomal dominant mutation
1 mutant allele is enough to cause OI phenotype
Shows up in nearly every generation (50% of chance in offspring)
what kind of disease is Supernumerary incisor
Autosomal recessive
what is needed for autosomal recessive diseases to show in the phenotype
2 mutant alleles to change phenotype
how does Autosomal recessive diseases show
not every generation, as both parents need to at least be a carrier of the gene
the processes of a generalized cell become specialized for a job
Cell differentiation
what changes in cell differentiation
size, shape, products, activities, divisions
what is the product that initiates differentiation
induction
an agent that procides cell with a signal to differentiate
Inducer
what must a cell be to respond to an inducer
must be competent to receive the signal
the ability of a cell to receive and respond to a molecular signal
Competence
what is needed for cellular competence
Receptors
Internal machinery
what inducer binds to cell surface BMP receptor type I or II
Bone Morphogenetic protein (BMP)
what inducer binds to intracellular vitamin D receptor
Vitamin D
What inducer binds to cell surface LRP6 and Frizzled Receptor
WnT signal
what is cell signaling
Transfer of information to cuase change in cell gene expression and function
what are some cell signals
Signals
Growth factors
Inducer
Ligand
types of cell signaling receptors
Membrane
Intracellular/nuclear
what happens in cell signalling
Inducing signal comes from outside cell
Cell is competent to receive it
Intracellular changes
Cell function changes
Effects of cell signaling
Cell Differentiation
Cell Proliferation
Cell Migration
what is cell signalling
Secreted chemical signal directs changes in target cells that express receptors
what controls gene expression
Transcription factors
what are transcription factors
Proteins that control whether genes will be transcribed into mRNA
how many genes can one TF control
tens to hundgreds of genes
what do TF do for target genes
can activate or repress expression
what are Pleiotropic effects
1 mutations causes lots of systems to be affected
Amino acids in the DLX family
214 amino acid TF
what does a a mutation in DLX3 lead to
Pleiotropic effects
what does DLX3 regulate
Hair folicle differentiation (BMP signaling)
Enamel genes (Amelogenin, Enamelin, Kallikrein 4)
Bone (formation, resporption, hemostasis)
what mainly happens in weeks 0-4 of development
mostly proliferation and migration
what happens in week 4 to 8
cell differentiation
Morphogenesis
Formation of major external and internal structures
Morphogenesis
what happens in week 8 to 40
Growth and maturations
what are the 2 stages of prenatal development
Embryo(0-8 week)
Fetus(8-40 week)
the inner cell mass of the Blastocyst stage
Embyroblast
what does the Embryobalst form
All tissues of the embryo
what are the cells of the embryoblast
Embryonic stems
the outer cells of the blastocyst
trophoblast layer
when is the Morula
3-4 days
what does the Blastocyst form
day 5-13
what are the layers of the Bilaminar embryo
Ectoderm- dorsal
Endoderm- ventral
what do he ectoderm cells look like
Columnar cells
What do the endoderm cells look like
More cuboidal
how does the mesoderm form
Ectodermal cells converge to the midline to form the primitive streak
Extoderm migrate through the streak between the ectoerm and endoderm to create the mesoderm
what is the conversion to a trilaminar embryo
Gastrulation
when does gastrulation occure
3rd week
what layers make up the buccopharyngeal membrane
Extoderm and endoderm without any mesoderm
what eventually forms the notocord
Cephalic (more rostal) migrating cells
when does Rostro-caudal(front back) folding occure
week 4
why does Rostro-caudal folding occur
directed growth at both ends
when does lateral (side to side) folding occure
week 4
what happens in lateral fodling
middle parts grow upwards and close to form the neural tube and neural crest cells
lateral parts of the ectoderm grow downwards to sournd the endoderm
what does Rostral-caudal folding form
A mouth
The primitive oral cavity
Stomatodeum
what defines the most rostral boundry of the primitive gut
Buccopharyngeal membrane
what origin are neural crest cells
Extoderm
where are neural crest cells formed
Adjacent to neural tube to separate from the neural plate when the neural tube closes
when does the neural tube close
day 22/end of 3rd week
what do the Neural crest cells do
Migrate and differentiate extensively
what do Cranial Nueral crest cells undergo
Epithelial- mesenchymal transformation
other name for Crnail neural crest cells
Ectomesenchymal cells
why are Cranial neural crest cells also called ectomesenchymal cells
Act like mesenchyme to form the connective tissues of the head
what part of Cranial neural crest cells is important to dentist
Create the connective tissue of teeth and supportive tissues
why are neural crest cells important
Become some of the craniofacial bones Cranial and sensory ganglia and nerves Adrenal medulla dentin Periodontal ligaments Alveolar bonds
where do skeletal bones come from
Mesoderm
where do Neural crest cells populate
head and oral cavity
what does the neural tube do during brain development
expands to become to forebrain, midbrain, and hindbrain
what does the hindbrain form
8 rhombomeres (buldges)
what do the Rhombomeres define
the origins of distinct populations of NCCs
what controls Neural crest cell migration
Tightly controled by signals
what neural crest cells contribute to branchial arch 1
From midbrain and Rhombomeres 1 and 2
First stream of neural crest cells from the midbrain and rhombomeres 1 and 2 contibute to what
The embryonic connective tissue of the face
the second stream of neural crest cells from the midbrain and rhombomeres 1 and 2 contibute to what
the embryonic connective tissues of the First branchial arch
what do Rhombomeres 3 and up contribe to
To other strucutures not the face or 1st branchial arch
what Rhombomeres express Hox TFs
NCC from rhombomeres 3 and up
what are Hox TF genes
Ancient rostral-caudal patterning genes that define body segments
why does the Craniofacial region not have Hox genes
it is a more recent evolutionary strucutre so it has its own set of TFs
what are Hox Free NCCs
NCCs that migrate from mid-brain and rhombomeres 1 and 2 to the face and first brnachial arch
what do all transciprtion factors include
a DNA binding domain that allows them to interact with genes
what is included in Homeobox TFs
Have a specific 180 base pair homeobox with specific sequences
what are HOX TFs a part of
a subset of Homeobox genes that are very ancient body patterning directors
what are the NCC body patterning Genes
The head organizes (NO HOX)
what patterning TFs direct craniofacial development
Otx2: orthodenticle homeobox 2
Msx: muscle segment homeobox
Dlx: Distal-less homeobox
Barx: barH-like Homeobox
what do NCCs contribute to in the branchial arches
Contribute to the mesoderm
what separates arches externally
Groove/cleft
What is the internal depression on a arch
Pouch
what makes up the the arch
NCC, mesoderm
what makes up a groove
Ectoderm
what makes up a pouch
Endoderm
what does Brnachial arch/groove//pouch 1 make
Mandible and maxialla (teeth)
Outer and middle ear
How do we understand the head organizer genes
Mutate mice (Dlx1/2) to show that altered craniofacial morphology and lack of maxillary molars
what does Dlx1/2 affect
teeth in maxillary process of BA1
what is treacher-collins syndrome
Underdeveloped craniofacial region and mandible
what causes Treatcher-collins syndrome
Failure/impairment of NCC migration to facial region due to a mutation in TCOF1, POLR1C, or POLR1D
what drives tooth formation
Epithelial-mesenchymal interactions
why is understanding tooth formation important
The epithelial-mesenchumal interactions for formation is conserved for many extodermal organs (hair, mammary gland, Feathers)
stages of ODontogenesis
Placode - bud - morphogenesis
what is essential for a tooth organ to form
Both adjacent tissues are essential for proper formation
what kind of signalling is done in Epithelial-mesenchymal sinaling
Reciprocal
Reiterative
Sequential
what is Reciprocal signalling
E-M signals back and forth
Reiterative signalling
Cells use same signaling pathways again and again at different stages
What are the major signalling pathways for Epithelial-mesenchymal signaling
BMP, FGF, SHH, WNT
what is sequential signalling
Orderly sequence of events determine whether cells are ready to receive the signal and how they respond
when does the stomatodeum develop
26th day
when does Odotogenic epithelium form
27th day
what are the nasal pits bound by LNP, MNP
34th day
when is fusion of the face complete
38th day
when does the processses of fusing occure with the dental lamina stage initiating odontogenesis
6th week (36 day)
what happens with the primary epithelial band forms
Proliferation of epithelial cells
Altered orientation of axis of division
Formation of dental lamina and 20 dental placodes
what is the dental lamina
Odontogenic bands
what are dental placodes
Local thickening of ectoderm for primary teeth
what is the main thing that occurs in the dental lamina
Proliferation
what tissues hold the odontogenic potential for the dental lamina stage
First epithelial factors direct odontogeneis ( we’ll make a tooth)
then mesenchymal signals take over ( we’ll make a molar)
what happens if you combine odontogenic epithelium with 2nd BA mesenchyme
Together they still form a tooth
If you combine molar mesenchyme with incisor epithelium
Form a molar shaped tooth
what are the theories for tooth type determination
Field model
Clone theory
what is the field model for tooth type determination
Epithelial signals (BMP, FGF) induce mesenchymal expression of TFs Mesenchymal TF expression in overlapping domains
what is the clone theory of tooth development
Each tooth type is derived from a close of mesenchymal cells programmed by epithelium
When close of cells reaches a critical mass, a tooth bud initiates
Next bud does not initiate until clone moves outside of inhibitory zone
what occures in the bud stage of odontogoensis
Down growth of dental lamina into a bud
Up growth of mesenchyme packing into a condensation
what occurs mainly during the bud stage
Proliferation
what is the condensed ectomesenchyme in the cap stage
Dental papilla
what is the surrounding ectomesenchyme in the cap stage
Dental follicle
what occurs in the cap stage of odontogenesis
PRoliferation and morphogenesis
What is part of the tooth germ
Enamel organ
Dental follicle
Dental papilla
what is the signaling in the cap stage
The Piary ENamel knot
what mkaes up the primary enamel knot
Non-dividing enamel organ cells in the cap stage
what does the Primary enamel knot express
Numerous signaling molecules
what does the Primary enamel knot direct
Proliferation of surrounding epithelial cells
what is the Primary enamel knot essential for
Bud to cap transition by regulating cap morphology
why does the Primary enamel knot dissappear
Apoptosis
Components of the enamel organ at the bell stage
Outer enamel epithelium
Inner enamel epithelium
Stratum intermedium
Stellate reticulum
what type of cells make up the outer enamel epithelium
Cuboidal cells
what type of cells make up the inner enamel epithelium
Columnar cells
what cells make up the stratum intermedium
2-3 cells thick layer adjacent to IEE
what cells make up the stellate reticulum
Star-shaped cells with spaces between them
what occures during the bell stage
Proliferation
Morphogenesis
Differrentiation
what does the signaling in the bell stage
Sexondary enamel knots
what is the secondary enamel knots
Non-dividing enamel organ cels in the bell stage that appear at the sites of cusps(not th incisors)
what do Secondary enamel knots express
Signaling molecules (FGF4)
what do the secondary enamel knots do
Direct proliferation of surroudning epithelial cells, IEE completes folding, determines number and location of cusps
what does the secondary enamel knot stimulate
stimulates terminal differentiation of odontoblasts to begin dentinogenesis
where does Dentinogenesis begin always
at the cusp tip
Dental Papilla becomes
Odontoblasts
IEE becomes
Ameloblasts
where are the zone of maturation
the very cusp tip
Anodontia
Absence of all primary or secondary teeth (tooth agenesis)
Oliogodontia
6+ missing teeth
Hypodontia
1-5 missing teeth
Hyperdontia
More than the normal number of teeth
why do dental anomalies exist
Disruption in epithelial or mesenchymal function in early stages of odonotogensis
what causes Oligodontia
Autosomal dominant mutation in PAX9 transcription facts
where is PAX9 expressed
In dental mesenchyme early in development
what are people with oligodontia missing
Missing maxillary and mandibular 2nd and 3rd molars (incisors less affected)
the mineralized tissues in the oral cavity
Enamel, dentin, cementum, bone
The process of making a composite material
Biomineralization
the organic component of enamel
Enamel-specific Proteins
The inorganic component of all things in the oral cavity
Hydroxyapatite
CElls for the enamel
Ameloblasts (ectodermal)
Organic component of dentin
Collagen
Organic component of cementum
Collagen
ORganic component o bond
Collagen
Cells of the dentin
Odontoblasts(mesenchymal)
Cells of the Cementum
Cementoblasts (mesenchymal)
Cells of bone
Osteoblast (mesnchymal)
what makes up 90% of the matrix of dentin, cementum and bone
Type I collagen
what directs mineral initation,deposition, and growth in dentin, cementum, and bone
Fibrillar collagens
Shape of HAP in bone dentin, and cementum
Plate like “habit”
Length and width of Bone, dentin, cementum HAP
W: 12-20nm
L: 20-50 nm
shape of enamel HAP
Elongated
width and length of Enamel HAP
Greater the 10x W and L
wy is biomineralization highly regulated
Don’t want Ca and P to be in blood and tissues
Need to trasnport ions to site of mineralization
Deposite extracelular matrix
hard tissue removal/remodeling
what is the roll of other matrix proteins in biomineralization
Positively and negatively regulate mineral initiation and growth
Result of Biomineralization regulation loss
Hypomineralization (Too little mineral)
Hypermineralization (ectopic Mineral)
Hypomineralization leads to
Poor bone growth
Thin, weak bones and teeth
Fractures, abscesses…
Hypermineralization leads to
Inappropriate mineralization of soft tisues
Debilitating and lethal
FTC and ACDC/CALJA
the ability to differentiate to all 3 germ layers
Pluripotent
Pros of Embryonic stem cells
Pluripotent
Divide indefinitely
can make any tissue and repair any defect
cons of embryonic stem cells
Control induction
Teratoma tumor formation
Ethical concerns
The ability to differentiate within lmits
Multipotents
Pros of Adult stem cells
Ability to make several types of tissues
Easier to control
Cons of Adult stem cells
Only Multipotent
Divide asymmetrically (not indefinitely)
quality and quantity decrease with age
where are dental stem cells found
Dental pulp
Deriodontal ligament
Dental follicle
Apical papilla