Final Exam Flashcards
What are the three main cytoskeletal components?
- Microfilaments
- Intermediate Filaments
- Microtubules
Microfilaments:
Composed of Actin, 6-8 nm in diameter, structural function, gives shapes to cells, and forms tracks for myosin, giving contractility.
Intermediate Filaments:
Vimentin (mesenchymal origin) and cytokeratin (epithelial origin). They are around 10 nm in diameter, and they anchor and help with structure, but are non-contractile. Tonofilaments are another word for intermediate filaments in epithelial cells, and they insert into desmosomes and around the peripheries of cells.
Microtubules:
Around 25 nm in diameter. Made of tubulin. They compose the monorail system (kinesins) and cilia and flagella (dynein). They help form the motor protein complex around the tubulin.
What are the 6 types of cell attachments?
- Tight junctions
- Zonula Adherens
- Focal Adhesion
- Desmosomes
- Hemidesmosomes
- Gap Junctions
Tight Junctions:
Made up of claudins, occludin, JAM, and they bind to actin microfilaments and serve as very narrow gaps between cells to control movement of stuff.
Zonula Adherens:
These hold cells together, remember that. Made up of cadherins on the outside and cantinins on the inside. The cadherins are Calcium dependent. They have vinculin and actinin attachments to actin filaments. Remember that zonula adherens bind to actin filaments, not intermediate filaments. Gaps of 20 nm.
Focal Adhesion Junctions:
These hold cells to extracellular matrix, and are similar to Cell-Cell adhesions. So here the cells are sticking to the matrix, as opposed to another cell (or actin). Integrins replace cadherins here and interact with many ECM proteins like collagen.
Desmosomes:
These are Cell-Cell adhesion. Cadherins are on the outside, and are called desmoglein and desmocollin. Catinins are on the inside and start with plako or desmoplakin. They attach to intermediate filaments, remember that. They have gaps of 25 nm, and hep resist shearing forces.
Hemidesmosomes:
These are cell to matrix adhesion, similar to focal adhesions, but they look more like desmosomes. These attach to intermediate filaments like desmosomes. They tightly attach to basal lamina by integrin-laminin and collagen XVII. They help resist shear as well.
Gap Junctions:
These are cell-cell aqueous pores. 6x connexins = 1x connexon. They form a 2nm pore, and have 2-3nms between cells. Ions and small molecules pass through but nucleic acids, sugars, and proteins are too large.
Basal Lamina:
ECM sheet attaching epithelium to connective tissue. Hemidesmosomes are here. It is 50-100nm thick. It has three zones. From top to bottom: Lamina Lucida (laminin, integrins), Lamina densa (collagen IV), and Lamina fibroreticularis (collagen III).
Fibroblasts:
They are the main cell in connective tissue. Highly motile, involved in tissue repair. Rarely have cell to cell connections, only exception is PDL. They often have cytoskeletal (actin) connections from integrins to fibronectin. Dental pulp is mostly collagen 3, and there are mainly fibroblasts there.
Collagen:
It is a triple helical structure, and is the most abundant protein in the body. It is rich in proline and lysine. Dentin is mostly type I collagen, some type II. Pulp is a mixture of collagen type I and collagen type III, and Cartilage is type II collagen. It is stacked with 5 microfibrils and a 1/4 stagger. In bone/dentin, mineral is deposited in the gap regions. Scurvy has to do with Vitamin C, specifically, prolylhydroxylase.
Elastin:
Is a fibroblast product. Assembled into sheets or fibers. Fibrillin-1 and fibirillin-2 which are glycoproteins form a microfibril scaffold onto which elastin fibers accumulate. Marfan’s syndrome is a fibrillin-1 mutation.
Connective Tissue Ground Substance:
Made up of mainly proteoglycans and glycoproteins. It is the “non fibrillar” stuff that makes up the rest of ECM. It is highly hydrated, sequesters fluid, gives compressive strength to tissues.
Proteoglycans:
Is made by fibroblasts, and is a main component of ground substance. They are protein cores with glycosaminoglycan chains (GAG). And GAGs are disaccharide units. But proteoglycans have relatively strong negative charges and are hydrophilic. Hyaluronic acid is an example. Perlecan and syndecan are examples of non-aggregating proteoglycans. But proteoglycans serve to sequester growth factors in ECM and can help activate GF receptors.
Glycoproteins:
These are proteins with carbohydrate side chains attached. They are found everywhere, but also in ground substance. Fibronectin, thrombospondin are both examples. Proteoglycans are technically specialized glycoproteins, and proteoglycans generally have a larger carbohydrate component than protein.
How is ECM digested?
With MMPs. As well as intracellular matrix.
What guides organogenesis?
Epithelial-mesenchymal interactions.
Which interactions dictate morphogenesis and differentiation? Cell-Cell or Cell-Matrix.
Cell-Matrix
What is ectomesenchyme?
It is embryonic connective tissue. Neural crest cells generate ectomesenchymal derivates like bone, dentin, cementum, periodontal ligament.
What is the stomatodeum covered with?
Primitive epithelium
What are the primary epithelial bands?
They are layers of thin ectoderm that become denser over time.
What forms the dental lamina?
In oral epithelium, cell proliferation causes thickening, invaginates into the basement membrane, and becomes dental lamina. Mesenchyme is found underneath the tooth bud/dental lamina. The primary epithelial band and the dental lamina represent where the teeth start growing.
What are the six stages of Crown development?
- Initiation - induction
- Bud stage - proliferation
- Cap stage - proliferation, differentiation, morphogenesis
- Bell stage - proliferation, differentiation, morphogenesis
- Apposition stage - induction and proliferation
- Maturation stage - maturation
Initiation Stage:
Induction is the process whereby one tissue changes the development of surrounding tissues.
Bud Stage:
At ten locations along each dental lamina, proliferation of epithelium produces buds. Each bud is the precursor of the enamel organ for each deciduous tooth.
What are the layers of a developing tooth in the bell stage from outside in?
Dental epithelium, Outer dental epithelium, enamel organ, stellate reticulum (rich in GAGs, supports enamel production), stratum intermedium (which is rich in alkaline phosphatase, and important in mineralization), inner dental epithelium (which gives rise to ameloblasts), dental papilla, dental follicle.
Cap stage:
Ectomesenchymal cells condense around developing cap, and these become the dental papilla and dental sac. The tooth germ = enamel organ + dental papilla + dental sac. Successional dental lamina forms on lingual side of dental lamina.
What is the dental sac?
It is made up of the dental papilla and all of the mesenchyme.
What is the enamel knot?
It is found just north of the dental papilla, on the other side of the inner enamel epithelium. We believe that the enamel knot is the signaling center, has many genes that control the shape of the tooth, growth factors play a role as well.
At what stage are the four distinct layers of the developing tooth formed?
The bell stage. Continued differentiation of enamel organ produces four distinct layers with different functions:
• Outer enamel epithelium.
• Stellate reticulum.
• Stratum intermedium.
• Inner enamel epithelium.
Also, during the bell stage, the cervical loop is formed, which is the junction of the OEE and IEE, and it is epithelium that will determine the shape and size of the roots of the tooth, and will become future CEJ.
Apposition stage:
This is the stage when the organic matrix of enamel and dentin are laid down followed by initial calcification. The order goes like this: IEE cells differentiate into preameloblasts, so these cells become polarized. Then preameloblasts induce outer dental papilla cells to differentiate into preodontoblasts which continue differentiating into odontoblasts. So IEE becomes ameloblasts, and outer dental papilla cells become odontoblasts. Enamel secretes down and dentin secretes up, both towards the DEJ. The first layer of dentin is produced and that sends signals to the ameloblasts to form more and secrete enamel. The DEJ forms after disintegration of the basement membrane. Prismless enamel is formed by early secretory ameloblasts. Enamel prisms are formed by Tomes processes of late secretory ameloblasts. Odontoblasts begin to secrete organic matrix of dentin- predentin. Predentin induces differentiation of preameloblasts into ameloblasts. Ameloblasts begin secreting enamel matrix which immediately calcifies to 25% of full mineralization.
Where is Tome’s process found?
It is the part on the ameloblast that sticks out toward the dentin. And the odontoblasts has a odontoblastic pocess that sticks into the enamel matrix that gives the tooth vitality in the future.
Where does the dental lamina come from?
It comes from the ectoderm lining.
What two things come from the ectoderm of the arch?
Tooth germ and ectomesenchyme from neural crest.
What three things come from the tooth germ?
Enamel organ, dental papilla, dental follicle/sac.
What gives rise to the root form of a tooth.
Hertwig’s root sheath, which came from cervical loop, which came from enamel organ.
What gives rise to enamel?
Ameloblasts, which came from the inner enamel epithelium, which came from the enamel organ.
What gives rise to dentin?
Odontoblasts, which came from dental papilla.
What gives rise to pulp?
Undifferentiated mesenchyme cells and fibroblasts, which came from dental papilla.
What three things does the dental follicle/sac give rise to?
Cementum (cementoblasts), PDL (fibroblasts), Alveolar bone (osteoblasts).
What are the seven stages of an ameloblast life cycle?
- Inner enamel epithelial cells
- Pre-ameloblast
- Initial secretory ameloblasts (no tomes process, prismless enamel)
- Secretory ameloblast (tomes process, emamel prisms)
- Smooth ended maturation ameloblast (removal of protein and water
- Ruffled ended maturation ameloblast (introduction of inorganic material
- Protective ameloblasts (enamel cuticle)
Maturation stage:
– After deposition and initial mineralization of enamel, secretory ameloblasts lose Tomes process.
– Maturation ameloblasts differentiate and remove some enamel proteins and water, and pump additional Ca++ into the matrix.
– Final differentiation of ameloblasts into protective ameloblasts.
– Basal lamina type material (enamel cuticle) secreted and ameloblasts attach to enamel surface via hemidesmosomes.
– This will become the epithelial attachment after eruption. – Reduced enamel epithelium (REE) forms after enamel is
fully matured.
– REE consists of OEE, IEE and intervening remnants of the other two layers of the enamel organ (stellate and stratum).
What is mantle dentin?
It is the initial layer of dentin next to DEJ. It has higher mineral content and its collagen fibers are perpendicular to the DEJ. The remaining dentin around pulp is called circumpulpal dentin, and this has lower mineral content with fibers parallel to DEJ.
What is root dentin and epithelial rests of Malassez?
The REE grows apically and eventually becomes HERS. HERS then induces dental papilla outer cells to become root odontoblasts, which then secrete predentin. HERS then detaches from root dentin and disintegrates, and remnants are considered epithelial rests of Malassez. Also, remember that roots are not complete until after the tooth has erupted and is in function.
How is cementum formed?
Dental sac cells migrate in and contact new root dentin surface and there is induction of dental sac cells to differentiate into cementoblasts, which secrete organic matrix called cementoid on new dentin surface, which eventually mineralizes into cementoid. In the apical 1/2 to 2/3 of root, cementoblasts become entrapped in lacunae as cementocytes.
Where does the PDL come from?
Dental sac ectomesenchyme cells differentiate into fibroblasts, which secrete collagen fibers, which become anchored in cementum as it is deposited by cementoblasts.
Where does alveolar bone come from?
Dental sac ectomesenchyme cells differentiate into osteoprogenitor cells then osteoblasts and lay down bone. And developing collagen fibers of the PDL become anchored in alveolar bone.
What are the four classes of signaling factors with tooth development signaling?
Oral ectoderm, dental placode, enamel knot, and secondary enamel knots. Some of these transcription factors stay inside, while the other ones are called growth factors and they can leave the nucleus. Transcription factors are found in all cells.
What are the two theories of tooth development?
- Field Theory (the cells migrate down and they don’t know what they are yet and they are influenced by molecules in the field or transcription factors)
- Clone Theory (the cells migrate down and they know where to go, molar, cuspid, incisor, and all have their own clones. The bicuspid is a hybrid.
- And the zone of inhibition just makes sure that we don’t have extra teeth popping out all over our jaw, it makes a boundary of where teeth can form.
Table of when epithelium and stages are inductive and will grow teeth:
With the lamina and bud stage, dental epithelium is the inductive one. So if you have tooth epithelium from the lamina or bud stage and combine it with other mesenchyme, you will grow a tooth. And during the cap and bell stage, dental papilla mesenchyme is the inductive one. So if you have tooth mesenchyme and combine it with other epithelium, you will grow a tooth.
What is the nerve, artery, muscles, and bones associated with the 1st arch?
Nerve - Mandibular Nerve
Artery - Maxillary
Muscles - Mastication (temp, mass, pterys), Mylohoid, anterior belly of digastric, tensor palati and tympani
Bones - Maxilla, Mandible, Malleus, temporal bone, zygoma, incus
What is the nerve, artery, muscles, and bones associated with the 2nd arch?
Nerve - Facial Nerve
Artery - Corticotympanic
Muscles - Facial expression, posterior belly of digastric, Stapedius, Stylohyoid
Bones - Stapes, Styloid process, upper half and lesser horns of hyoid
At what week does central face development happen?
At week 4. This is when nasal placodes start to develop and thicken, and you get a proliferation of ectomesenchyme on both sides of each placode resulting in the medial and lateral nasal processes.
How is the upper lip formed?
It is formed at 6 weeks and the medial nasal processes merge with each other as well as the maxillary processes of the first brachial arches to form the upper lip.
What are the primary and secondary palates formed from?
Primary - merger of the medial nasal processes
Secondary - formed from the maxillary processes of the first branchial arches
What is cleft lip and what causes it?
It is defective fusion of the medial nasal processes with the maxillary process. 80% of cases are unilateral.
What is cleft palate and what causes it?
It is a failure of the palatal shelves to fuse, and the minimal manifestation of it is a bifid uvula. The majority of cases are Cleft Lip + Cleft Palate together, and then Cleft palate alone, and finally Cleft lip alone.
Syndromic clefts:
There are more than 350 syndromes that can causes orofacial clefts. 30% of patients have CL + CP, while 50% of patients have Cleft Palate only. So with syndromes, it is more common to just have Cleft palate rather than both. Pierre Robin sequence is an example of cleft palate only syndromic problem, with mandibular micrognathia and downward discplacement. Nonsyndromic clefts can happen from folic acid deficiency, maternal alcohol or cigarette, corticosteroid use, etc.
What is lateral facial cleft?
Lack of fusion of the maxillary and mandibular processes.
What is oblique facial cleft?
Failure of fusion of the lateral nasal processes with the maxillary process. Upper lip to the eye, and almost always associated with CP.
What is a median cleft of the upper lip?
Failure of fusion of the medial nasal processes, very rare.
What type of race gets Cleft Palate the most?
Native Americans, then Asians, then Caucasians. CL + CP is more common in males, while CPO is more common in females.
What is it called when an indent appears in the very middle on the posterior hard palate margin, appears as a bluish midline discoloration, and the surface appears intact?
A submucous palatal cleft.
To treat cleft lip, what three things must you pass?
Rule of 10. 10 weeks old, 10 lbs, and 10gm %HM.
What are lip pits most commonly associated with?
Syndromes, they are usually bilateral. van der Woude syndrome is the most common cause of paramedian lip pits., also has CL + CP and is most common form of syndromic clefting.
What is microglossia?
Abnormally small tongue. Frequently associated with hypoplasia of the mandible. Lower incisors may be missing. Usually syndromic.
What is it called when the tongue has a short, thick lingual frenum resulting in limitation of tongue movement?
Ankyloglossia. Happens four times more in males, may cause problem with speech and breastfeeding, no treatment if asymptomatic. Frenuloplasty, wait until age 4-5.
What is a lingual thyroid?
Thyroid gland begins as epithelial proliferation in the floor of pharyngeal gut during week 3-4, and during 7, the thyroid bud descends into the neck, and forms foramen cecum in tongue, just next to terminal sulcus, but if it doesn’t descend ectopic thyroid can be found there. Seven times more common in females, symptoms arise during puberty, pregnancy.
What is a thyroglossal duct cyst?
From epithelial remnants of the thyroglossal tract.
Which part of tooth does not have a mesenchymal origin?
Enamel. It has an ectodermal origin and is a product of the enamel organ.
Properties of Mature Enamel:
Acellular, Non-vital, non-vascular, 2.5mm at crown, 94% inorganic, 1% organic, and 3% water. No collagen in enamel. Inorganic component is Hydroxyapatite (HA).
Major enamel proteins:
Amelogenins, ameloblastins, enamelin, tuftelin.
Enamel Crystals:
Hydroxyapatite, but lots of enamel crystals are actually carbonatoapatite, when CO32- substitutes for either PO43- and OH-. Carbonate and magnesium incorporate into the inner enamel, while fluoride in the outer enamel. The enamel crystals are very long, run the entire length of the enamel layer. Hexagonal symmetry increases as crystals mature, but fully mature crystals lose their shape.
Enamel Rods:
They do not reach dentin. They are cylindrical accumulations of enamel crystals lined up along the long axis of the rod. They run perpendicular to the DEJ. Often called prisms. 1 ameloblast = 1 rod. At the center of the rod, they run completely parallel, and then flares out towards the bottom because the rod sheath only goes 3/4th the way around and ends.
Rod Sheath:
A space that fills with proteins and organic material and surrounds the rods. Ameloblastins and amelogenins are found here.
Interrod Enamel:
Same basic composition of rods, fills the gaps between the rods, it is all continuous with itself. It is 1 ameloblast per 1 rod, but 1 rod has four other ameloblasts contributing to it. The crystal orientation is different and opposite between rod and interrod enamel area. Caries are thought to penetrate through the higher protein rod sheath areas, thus between rod and interrod enamel.
Formation of Enamel:
Inner Enamel Epithelium, formation of first pre-dentin by odontoblasts, and ameloblasts are activated and deposition of enamel takes place. Initial deposition only around 30% mineralized, and as it matures, organic component reduced, and mineralization increases. Ameloblast maturation occurs in three phases: 1. Pre-secretory = mature from pre-ameloblasts to ameloblasts. 2. Secretory = deposition of enamel. 3. Maturation = reduction of organic matrix, increase mineralization via ion transport. Longest phase of enamel growth.
Deposition of Enamel:
Ameloblasts deposit organic matrix via secretory vesicles, which exit the cell apically. Tomes process is the site of much secretory activity. Ameloblasts are bound together by junctional complexes. Initial enamel in apposition to dentin does not have a rod arrangement, it is uniform. Tomes process forms the enamel rod structure, the distal of it towards the forming enamel, and the proximal is towards the stratum intermedium. Interrod enamel forms first, and forms a groove into which rods are formed. Eventually, tomes process retracts and outer rods are straighter and the final enamel is formed without rods. Thus Tomes process kind of equals rods.
Maturation of Enamel:
The loss of stellate reticulum and fusion of the OEE and IEE result in Reduced Enamel Epithelium (REE). Maturing the enamel is getting rid of the protein content and water, increasing mineralization, pumping in calcium ions to build HA crystals for mineralization. Can take up to 5 years for some permanent teeth. Modulation is the name by which water and proteins are removed. We have ruffled cells and smooth cells with enamel maturation. Ruffled cells is secreting things into enamel, secretes proteoltyci enzymes like MMP to chop up the proteins, and lowered pH favors mineralization. Smooth cells is letting things out of ameloblasts, allowing diffusion of protein fragments out of enamel, which leak in between cells and laterally diffuse through cell layer.
What is the fate of the enamel organ?
Fuses to form REE. So enamel organ remnants have fused with the oral eptihelium, forming a covering over the tooth. Nasmyth’s membrane is the debris that remains on crown after eruption. The primary enamel cuticle is the last secretory product of the ameloblasts and is a mineralized coating. The secondary enamel cuticle or dental cuticle is formed from the remains of the REE merged with the oral epithelium and is removed due to the mechanical forces, it can be removed by toothbrushing.
Which rods are staighter? Outer or Inner enamel rods?
Outer 1/3rd are much straighter, the inner are somewhat interwoven.
Tomes process is present on maturation stage of ameloblasts. True or False?
False. While only its proximal portion is present on presecretory ameloblasts, and distal portion changes shape when the last third of enamel layer is being formed.
Interrod enamel forms before rod enamel. True or False?
True. It makes a pit into which the enamel rod is synthesized.
What are the main three proteins for enamel deposition?
- Amelogenins - main protein, only expressed while enamel is being produced (stop during maturation). Restricts lateral HA crystal growth. Loss of function = no enamel rods, very disorganized structures.
- Ameloblastin - Expressed at all times. Ameloblasts adhesion to developing enamel. Loss of function = ameloblasts fall off, no enamel.
- Enamelin - Least abundant protein (but largest). Only present at leading edge of enamel deposition. Loss of function = no enamel.
What are the two proteins of organic component degradation of enamel?
- Enamelysin - Is an MMP, chops up ameloblastin and enamelin. Loss of function = thin immature enamel. Critical for removal of organic component to allow for increased mineralization.
- Enamel Matrix Serine Protease - Degrades amelogenins. Loss of function = immature enamel.
What are the two proteins of basal lamina during enamel maturation?
- Amelotin
- ODAM
- The basal lamina with enamel doesn’t have any collagen IV (chicken wire), just ODAM and amelotin mainly.
What does enamel acid etching do?
It provides a better bonding surface by increasing the porosity of enamel surface, removing crap clinging to the enamel surface, and dissolving enamel crystals. Carbonated apatite is more vulnerable to acid attack than calcium and fluoride apatite, so the core is more vulnerable, acid etching dissolves from inside out.
What are the three types of enamel etching that can happen?
Type 1 = most common, removal of rods. (they are usually attacked first because they are sticking out and are more vulnerable, they are perpendicular to enamel surface.
Type 2 = Reverse of type I, removal of interrods.
Type 3 = Irregular and indiscriminate pattern.
Definition of enamel abrasion:
Removal of enamel by abrasive forces, like aggressive brushing.
