Embryo Development PDF

EMBRYO To consider the earliest stages of embryonic development from fertilisation to gastrulation Germ cell formation and fertilisation: - Somatic cell has 46 chromosomes - 22 homologous sets one sex each frm mother and father - Female XX - Male XY Fertilisation -- fusion of male an...

EMBRYO To consider the earliest stages of embryonic development from fertilisation to gastrulation Germ cell formation and fertilisation: - Somatic cell has 46 chromosomes - 22 homologous sets one sex each frm mother and father - Female XX - Male XY Fertilisation -- fusion of male and female germ cells Spermatoza -- sperm cell Ova -- egg cell Fertilisation leads to a zygote Diploid -- complete number of chromosomes in somatic cells Haploid -- half the number of chromosomes in gamete cells Miosis -- cell division of somatic cells -\> identical daughter cells Meiosis -- cell division in reproductive cells -\> half number of chromosomes from somatic cells Cell division: (mitosis) - DNA replicates during synthetic phase - DNA doubles -\> tetraploid - Divides equally btw new daughter cells - Prenatal development:  +-----------------------+-----------------------+-----------------------+ | **Stage 1 (0-4 | **Stage 2** | **Stage 3** | | weeks)** | | | +=======================+=======================+=======================+ | Cellular | Morphogenesis | Growth and maturation | | proliferation | | | +-----------------------+-----------------------+-----------------------+ | Cellular migration | Many intricate | | | | | | | | embryologic processes | | +-----------------------+-----------------------+-----------------------+ | Some degree of | | | | cellular | | | | differentiation | | | +-----------------------+-----------------------+-----------------------+ Induction, competence and differentiation: - Patterning important in development from initial axial (head to tail) specification of embryo in segmentation - Spatial and temporal event -\> starts induction, competence and differentiation - Can be used for teeth development and supporting tissues - Induction: process that initiates differentiation. Incudcer -\> agent that provides cells w signal to enter this process - Homeobox genes, growth factors and retinoic acids crucial to development ** To explore the events taking place in human development weeks 1-3 gametogenesis, blastocyst formation and gastrulation (formation of the trilaminar embryo)** Diagram of a uterus and fertilization process Description automatically generated Week 1:  - Fertilised egg -\> rapid divisions -\> ball of cells called morula - Fluid build up in morula and cell realignment -\> blastocyst (blastula) A diagram of a cell Description automatically generated Week 2: - Day 8 -\> cells of embryoblast differentiate into 2-layered disc -\> bilaminar disc - Ectodermal layer (dorsal) are columnar -\> reorganise to form amniotic cavity - Secondary yolk sac (ventral) aka, endothermal layer form roof of the second cavity)  WEEK 3: - Conversion of **bilaminar embryo disc (ectoderm + endoderm) -\> trilaminar embryo disc** - Begins w formation of **primitive streak** - Changes in cell shapes, rearrangement, movement and alterations in adhesive properties  Gastrulation: - Blastula -\> gastrula - Slight enlargement of ectodermal and endodermal cells - After **2 weeks**, axis of embryo is established - Plate (cranial)/prochordal end aka head end (rostral) - Tail (caudal) end is cecal plate Diagram of a mouse with a blue oval Description automatically generated - Cells go thru streak -\> change shape and divert from streak (lateral and cephalic directions) - Cells if epiblast break off and travel -\> primitive pit -\> epiblast layer -\> form 3 layers; endoderm, mesoderm + ectoderm Endoderm -- formed by epiblast cells migrated from primitive pit -\> displace hypoblast Mesoderm -- lie btw endo and ectoderm (intra and extraembryonic mesoderm Ectoderm -- remaining epiblast cells in place @ primitive pit ↑ these cells responsible for forming diff tissues of fetus Ectoderm: liver, pancreas, lining of urethra + bladder + reproductive system, epithelial lining of digestive+ respiratory tracts Mesoderm: notochord, MSK, muscle layer of stomach + intestines, circulatory system, respiratory system, outer lining of gut Endoderm: epidermis of skin, cornea + lens of eye, nervous system **To site the discussion in the context of well-known defects in embryological development such as Down's syndrome, Turner syndrome etc.** Defects include meiosis malfunction -\> abnormal number of chromosomes → congenital abnormalities → head and neck region including teeth Trisomy 21: - 24 chromosome gamete fusing w normal gamete resulting in zygote containing 47 chromosomes -\> extra chromosome - 21^st^ chromosome pair has 3 chromosomes → trisomic - Facial clefts, shortened palate, protruding + fissured tongue, delayed eruption of teeth Turner Syndrome: - Most common chromosomal disorders in femaes - Partial/complete missing X chromosome - Monosomy - Dysmorphic stigmata, short, sexual infantilism, renal + cardiac + skeletal + endocrine + metabolic abnormalities \~10% of mutations are caused by single gene malfunction - Autosomal dom: achondroplasia, cleidocranial dysostosis, osteogenesis imperfecta + dentinogenesis imperfect - Autosomal recessive: chondroecto dysplasia, cystic fibrosis ** To introduce the term 'epigenetic' and briefly discuss how genetic and epigenetic processes are important in regulating development even at this early stage** DNA methylation - Methyl group addition to cytosines via covalent modification - CpG region -\> clusters in promoter regions of target genes - Hypermethylation ↓ gene transcription - Hypomethylation ↑ gene transcription Histone modification: - Positively charged nuclear proteins that DNA wraps around - Modify these → transcription factors reg activity of promoters Non-coding RNA: - Cluster of RNA that doesn't encode func proteins - Can regulate expression of gene and chromosome to control cell diff Genetics -\> inheritance -\> traits and disorders Epigenetics -\> what genes are activated -\> chem modifications to DNA and proteins -\> when and where genes are active - **Understand Neural Crest formation and their final fate** 1. Nervous system development starts by ectoderm thickening at rostral (head) end -\> neural plate 2. Margins of plate raise -\> neural fold. Folds also make groove 3. Folds merge -\> neural tube 4. Thickens again and separates -\> forms floor of amniotic cavity  A close-up of a cross section of a human body Description automatically generated - Ant portion of neural tube expands -\> forms fore-, mid-, and hindbrain - Part associated w hindbrain develops 8 bulges -\> rhombomeres - Somitomeres contributes w head muscles SOMITES: Each somite has 3 parts: - Sclerotome: becomes 2 adjacent vertebrae + articulating discs - Myotome: origin to muscles - Dermatome: becomes connective tissue of skin RHOMBOMERES: - Midbrain + rhombomeres 1 & 2 make face and first branchial arch - NCC from rhombomeres 3 onwards make pharyngeal structures NEURAL CREST: - Group of cells @ dorsal margin of closing neural folds - Become separate from neuroectoderm - Receive inductive signals to undergo epithelial-mesenchymal transformation - Exhibit exceptional capacity of stem + progenitor cells - 3-4 week of embryo development NEURAL CREST CELL: - Signalling molecules (Wnt + FGF) are secreted by surrounding nonneural ectoderm - Induces neural crest cell cascade - Competence determined by expression of members of "Snail zinc-finger transcription factor family" -\> repress expression of cell adhesion molecule E-cadherin - Origin of most of connective tissue of head - Embryo connective tissue from ectomesenchyme - Proper migration essential for craniofacial skeleton + teeth - All tissues of tooth (EXCEPT ENAMEL + SOME CEMENTUM) from neural crest cells 1. Growth 2. Morphogenesis 3. Ceff diff 4. Pattern formation - **Explore branchial arches formation and developmental processes** A purple and white text on a purple background Description automatically generated - **Examine development of the face and related structures** - Week 4-10 - Interaction btw neural crest mesenchyme + sensory facial ectodermal placodes - Epithelial-mesenchymal interactions - Sequential activation of specific genes + signalling molecules  Week 4 ↑ A close-up of a baby\'s body Description automatically generated Week 5↑ Week 6: - 2 mandib processes fuse to form lower jaw - Max processes grow below lat nasal processes towards med nasal processes - Forms naso-optic furrows -\> nasolacrimal groove - Ectodermal rod of cells sink below surface -\> canalises to form nasolacrimal duct  - **Reveal development of the tongue and muscular structures** SECONDARY PLATE: - Distinction btw oral and nasal cavity after secondary plate formation - Happens btw week 7 and 8 - Done after \~3 months A diagram of a human body Description automatically generated A diagram of the human body Description automatically generated Head position is important in tongue development -\> at 9 weeks head is raised to allow tongue room to move forward TONGUE FORMATION: - Begins at 4 weeks of gestation - Lingual swellings + tuberculum impar (from first arch) form ant 2/3 of tongue - Hypobranchial eminence overgrows second arch - Pharyngeal arches meet in midline below primitive mouth - Develops alongside nerve of first arch - 7 week -\> intramembranous ossification -\> forms bone from existing cartilage - Bone formation spreads rapidly ant towards midline + post towards bifurcation of mandib nerve to lingual + inf alveolar nerve branches - Midline, medial + lateral alveolar plates of bone develop -\> forming tooth germs that subdivide through bone - Ramus develops by spread of post ossification into mesenchyme of first arch, turning away from Meckel's cartilage -\> divergence marked by lingula - Finishes by week 10 -\> Meckel's cartilage degenerates to make place for new bone - Further growth from 3 secondary cartilages: condylar (most important), coronoid, symphyseal cartilage CONDYLAR CARTILAGE: - Appears @ 12 weeks - Cone/carrot shaped mass in ramus - @ 20 weeks is thin on condylar head - Stays until late 20's MAXILLA DEVELOPMENT: - Centre of ossification alongside nasal capsule cartilage - Appears @ angle btw division of anterosuperior dental nerve + inf orbital nerve - Ossification spreads post towards developing zygoma + ant towards incisor region + sup to form frontal process - Zygomatic/malar cart appears in developing zygomatic process which is major to zygomatic dev - Max sinus dev at 16 weeks as shadow groove on nasal aspect TMJ DEVELOPMENT: - Initially formed from membranous centres of ossification - Broad band of undiff mesenchyme btw dev ramus of mandible + squamous tympanic bone -\> dense strip of mesenchyme as condylar cartilage forms - Adjacent mesenchyme forms joint cavity - Strip -\> articular disk - **Discuss clinical considerations and anomalies in facial development** Holoprosencephaly: - Forebrain fails to divide ito 2 separate hemispheres and ventricles - 1:10,000 - Unknown cause -\> chromosomal abnormality, gene mutation, maternal diabetes, infection, drugs? - Facial anomalies - Cyclops - Multifactorial aetiology -\> genetic + environmental disturbances - Disturbance btw week 6 +7 - Diff forms; median, bilateral, oblique, lateral, median mandib - Can be btw lip and palate -\> normal, cleft lip + alveolus, cleft palate 1^st^ arch syndromes: - Most congenital abnormalities of craniofacial region involve change in pharyngeal arch - Not enough migration of neural crest cells into 1^st^ pharyngeal arch in week 4 - Might be -\> decreased cell proliferation or increased cell death - Pierre Robin's sequence + Treacher Collins' syndrome Pierre Robin's: - Hetero birth defect - 1:8500 - Equal in male and female - Autosomal recessive hereditary -\> maybe X linked - Micrognathia, glossoptosis, ear defect, speech defects  Treacher Collins': - 1:10000 - Autosomal dom - Negative canthal tilt, micrognathia, absent/malformed ears, lip + palate clefts - Mutation of Tcof1 gene - Disrupts protein sysnthesis -\> treacle Environ factors for congenital defects: - Infection -\> rubella virus, treponema pallidum - X-ray - Cortisone - Hormones - Nutritional deficiency - Alcohol abuse Fetal Alcohol disorder: - Caused by drinking more than 4 units alcohol/day - 33% of kids w FAS have alcoholic mums - Dependent and related to time where foetus is exposed TOOTH EMBRYO 1 - To consolidate discussion on the structure of the dental hard tissues Enamel: - Origin: ectoderm -\> oral epithelium from ectoderm - Development: forms from structure called enamel organ (part of dev tooth gem). Ameloblasts derive from ectodermal lining of oral cavity Dentin: - Origin: mesoderm -\> from neural crest cells - Development: odontoblast derived from dent papilla (mesenchymal tissue from neural crest) Cementum: - Origin: mesoderm -\> from neural crest cells - Development: cementoblasts arise from dent follicle (neural crest) Dental pulp: - Origin: mesoderm (neural crest cells) - Development: from inner part of dent papilla -\> same place that odontoblasts come from PDL + alveolar bone: - Orgin: mesoderm (neural crest cells) - Development: comes from dent follicle A diagram of a structure Description automatically generated - To consider the role of epithelial-mesenchymal interactions in the induction of developmental processes  - Involves many growth and transcription factors for tooth dev - Require signalling btw oral epithelium + mesenchyme - Mesenchyme (neural crest cells) develops dent papilla + follicle - Epithelial cells (ectoderm) form enamel - To illustrate this with a discussion of the epithelial-ectomesenchymal interactions important in the induction of odontogenesis Signalling molecules: - FGFs: reg cell prolif, survival + differentiation in epithelium + mesenchyme - BMPs: promote odontoblast differentiation - Shh: tooth patterning, shaping of tooth germ Importance of epithelial-mesenchymal interactions: - Shape + size of tooth - Differentiation of cells into diff types (ameloblasts, odontoblasts, cementoblasts - Coordinating deposition of enamel, dentin + cementum Importance of Shh: - Marks future site of tooth development in dent placode - Triggers condensation of neural crest derived mesenchymal cells -\> forms dent mesenchyme - Reg formation of dent lamina - In bud stage, expressed lots in epithelial cells -\> growth + invagination of tooth bud - In cap stage shapes tooth germ + controls prolif of epithelial cells in enamel organ -\> defines regions of dev tooth (enamel rogan, dent papilla + dent follicle) - Involved in morphogenesis -\> shape determination -\> growth of cusps - Disruption in Shh -\> supernumerary teeth/missing teeth/abnormal tooth shapes - Helps dev Hertwigs epithelial root sheath (HERS) - Influences tooth eruption -\> remodels tissues around dev tooth Morphogenesis: shape of tooth from cell prolif + cell movement Histogenesis: differentiation of cells -\> fully formed dent tissues Tooth type = patterning of the dentition -\> spatially restricted expression of homeobox genes -\> SEK gene. - To describe the stages classically used to describe the histological progression of tooth development   Diagram of a diagram showing different types of teeth Description automatically generated Initiation stage: 6 weeks - Early tooth dev -\> oral epithelium signals to mesenchymal cells - Signals include: fibroblast growth factors (FGF), bone morphogenetic proteins (BMP) + sonic hedgehog (Shh) - Cause mesenchymal cells to condense -\> form dent mesenchyme -\> forms dent placode Bud stage: 8 weeks - Each dent lamina forms 10 buds (10 prim teeth/jaw) - Enamel organ is spherical/ovoid epithelial condensation - Epithelium invaginates into mesenchyme -\> tooth bud - Epithelial cells cause mesenchymal cells to continue proliferating + condense around bud -\> form dent papilla + dent follicle - Reciprocal signalling important for progressing tooth development -\> mesenchymal cells diff into odontoblasts + other structures Cap stage: 9-11 wekks - Cells proliferate and invaginates deeper to form cap - Epithelial tissue -\> enamel, mesenchyme -\> dent papilla + follicle - Enamel organ -\> ameloblasts -\> enamel - Dent papilla -\> odontoblasts -\> dentin - Dent follicle -\> cementoblasts -\> cementum + PDL - Intracellular space = glycosaminoglycans -  Bell stage: 11-14 weeks - Epithelial and mesenchyme interactions become more refined - Tooth germ takes on bell shape - Final differentiation of ameloblasts and odontoblasts -\> also start producing enamel + dentin - Basement membrane becomes dentino-enamel junction - Coordinated deposition of enamel + dentin - Enamel organ = 4 distinct layers -\> stellate reticulum, stratum intermedium, external enamel epithelium, enamel epithelium Crown formation: - Dentin produced first them signals ameloblasts to start producing enamel -\> tightly controlled - Allows tooth crown forms properly -\> enamel on outside protecting dentin Root formation: - After crown formation -\> epithelial root sheath forms (Hertwig) - Downgrowth of epithelial cells - Epithelial-mesenchymal interaction guide root dentin formation + cementum dev - PDL forms from mesenchymal cells in dent follicle from epithelial signal influence - To emphasise how a thorough knowledge of normal tooth developments essential to understanding what happens when it goes wrong enamel knot: - Localised, non-dividing cells at inner dental epithelium - Bulge into dent papilla - Signalling centre expressing growth factors -\> Shh, BMP, FGF, WnT - Affects crown morph Problem w bad Shh signalling: - Hypodontia: missing teeth -\> failure of tooth germ initiation - Supernumerary teeth -\> extra teeth -\> excessive Shh signalling/misregulation - Abnormal tooth size/shape - Enamel + dentin defect Morphogenesis molecular mechanisms - Position and patterning of dentition - Pattering determined by homeobox gene expression in ectomesenchyme -\> makes teeth and bones SEK: - Secondary enamel knot - Cells appear in middle stage of tooth dev - Guides cusp formation - Multicuspal teeth only PEK: - Primary enamel knot - All teeth - Early in tooth dev - Overall structure TOOTH DEV 2 - Consolidate knowledge on the structure of the dental hard tissues  - Histodifferentiation: diff btw ameloblast + odontoblast - Dentine = mesenchymal tissue -\> ectomesenchyme of dent papilla → neural crest origin - Dent formation = bell stage -\> organic matrix mainly collagen Dentinogenesis: 1. Diff of odontoblasts 2. Deposition of organic matrix 3. Mineralisation + modification of organic matrix 4. Peritubular + secondary dentine form 5. Tertiary dentine form in response to injury **1. Differentiation (Odontoblast Formation)** - **Origin**: derived from **neural crest cells**, migrate into the developing tooth\'s dental papilla (a group of cells in the tooth germ). - **Induction**: signals from the **inner enamel epithelium** (sig from ameloblast causes pre-odontoblast to diff) trigger cells in the dental papilla to differentiate into odontoblasts. Organelles ↑ size and number -\> esp golgi and rough ER - **Polarization**: become polarized, meaning they have a distinct orientation with a nucleus at one end and cytoplasmic extensions at the other (towards the future dentin matrix). Secretes matrix. **2. Dentinogenesis (Dentin Formation)** - **Initial dentin production**: begin secreting **predentin**, an organic matrix composed of collagen and other proteins.as matrix is laid down, odontoblast moves in opposite direction. After enough matrix is there = mineralisation. Starts from cusp tip to root. - **Mineralization**: This predentin gradually becomes mineralized into **dentin** by the deposition of calcium phosphate crystals, forming a hard tissue. The first layer of dentin formed is called **mantle dentin**, and subsequent layers are called **circumpulpal dentin**. - **Tomes' fibers**: extend long cytoplasmic processes, known as **Tomes\' fibers**, into the dentin they produce, leaving a tubular structure within the dentin called a **dentinal tubule**. OM of fully diff odontoblast: - type I collagen -- RIGHT ANGLE to dentine enamel junction - dentine sialoprotein - dentine phosphoprotein -- signal epithelial-mesenchymal interaction Secondary dentine: - pre-programmed age - potentially due to apoptosis -\> pulp volume decreases - dentine deposition = odontoblast die Tertiary dentine: - repeated trauma makes atubular and bonelike dentine - **3. Maintenance (Tooth Function)** - **Odontoblasts\' role in tooth health**: Once dentin formation is complete, odontoblasts continue to line the outer surface of the dental pulp. They remain active throughout life, producing small amounts of secondary (or regular) dentin to help protect the pulp and respond to stimuli, like wear or minor injuries. - **Tertiary dentin production**: In response to injury or decay, odontoblasts can produce **tertiary (or reparative) dentin**. This is a defense mechanism to protect the pulp from damage. **4. Aging and Degeneration** - **Reduced activity**: As the tooth ages, odontoblast activity decreases, and the production of secondary dentin slows. The odontoblasts themselves may shrink or lose functionality over time. - **Cell death**: Eventually, odontoblasts may undergo apoptosis (programmed cell death) due to aging or significant injury to the tooth. In some cases, damaged odontoblasts can be replaced by new cells called **odontoblast-like cells** derived from the dental pulp to continue producing reparative dentin. Amelogenesis: - Amelogenesis + odontogenesis occur almost simultaneously - Both begin at enamel-dentine junction **1. Differentiation (Ameloblast Formation)** - **Origin**: derived from the **inner enamel epithelium** of the enamel organ, which is part of the developing tooth germ. - **Induction**: signals from the underlying odontoblasts induce the inner enamel epithelial cells to differentiate into ameloblasts. This interaction between odontoblasts and ameloblasts is crucial for the initiation of enamel formation. REVERSE POLARITY - COLUMNAR - **Morphological change**: As ameloblasts differentiate, they elongate and become polarized, meaning their nucleus moves towards the base of the cell, while the part responsible for enamel secretion (Tomes\' process) is at the top. **2. Secretory Phase (Enamel Production)** - **Enamel matrix production**: Once fully differentiated, ameloblasts enter the **secretory stage**, during which they begin producing and secreting the proteins that form the **enamel matrix** (mainly amelogenin, ameloblastin, and enamelin). **4a = away from tomes** **4b = close to tomes** - **Tomes\' process**: helps organize the enamel crystals into the intricate structure of enamel prisms, giving enamel its strength and hardness. - **Mineralization**: begins to mineralize, and this process continues as the enamel matures. Ameloblasts ensure that minerals (calcium and phosphate) are deposited into the enamel matrix. Becomes pyramid as cell retreats. High nuclei have come down -\> increases SA - 50% of ameloblasts die - Lose tomes process when full enamel thickness reached **3. Maturation Phase** - **Enamel hardening**: switch from producing enamel matrix to actively transporting minerals (calcium) into the already laid-down enamel, helping it become fully mineralized and hard. critical for strengthening the enamel. - **Modulation**: alternate between two forms---**smooth-ended (5b)** and **ruffle-ended (5a)**---to regulate the transport of proteins and minerals into the enamel. This ensures proper enamel hardness and structure. - **Lasts 2**-3x longer than secretory phase - After maturation, shortens in height -\> protect enamel surface during eruption and form junctional epithelium **4. Protective Phase** - **Protective role**: Once enamel production is complete and fully mineralized, ameloblasts secrete an organic covering known as the **primary cuticle** on the enamel surface, which provides temporary protection for the newly formed enamel before tooth eruption. - **Formation of reduced enamel epithelium**: The ameloblasts then combine with other cells of the enamel organ to form the **reduced enamel epithelium**, which will cover the tooth as it erupts into the oral cavity, preventing enamel damage. **5. Degeneration and Death** - **Tooth eruption**: After the tooth erupts through the gums, the protective enamel layer is exposed to the oral environment. Ameloblasts, which are no longer needed, undergo **apoptosis** (programmed cell death) or are shed. - **No regeneration**: Unlike odontoblasts, ameloblasts do not persist after enamel formation and cannot regenerate. Once they are lost, the body cannot produce more enamel, which is why enamel damage (like cavities or erosion) is permanent. Enamel formation stage: **1. Initiation Stage** - **Ameloblasts form -\>** secrete enamel proteins on top of dentine matrix - Starts by dentine matrix formation - Differentiation of pre-ameloblast + resorbtion of basal lamina -\> begins at cusp tips then progresses cervically **2. Secretory Stage** - **Enamel matrix production**: Ameloblasts start secreting a soft, gel-like substance called the **enamel matrix**, which is made up of proteins and serves as the initial framework for enamel. This matrix later hardens into enamel. - 25-30% mineral by weight -\> soft translucent - Tomes process at distal secretory end A close-up of a section of a human body Description automatically generated **3. Transition Stage** - **Shift to mineralization**: ↓ the production of the enamel matrix and begin removing the matrix for mineralization (hardening). The cells also apoptosis and prepare to help with the mineralization process. Enamel proteins: \- less than 1% weight of mature enamel \- 25-30% weight of dev enamel \- MMP-20 + KLK-4 \- proteins include: amelogenin (90%), ameloblastin (5%) + enamelin **4. Maturation Stage** - **Enamel hardening**: Ameloblasts pump minerals, like calcium and phosphate, into the enamel matrix. These minerals crystallize and make the enamel hard and strong. During this stage, the enamel matures and becomes fully mineralized. - **Young enamel = 65% water, 20% organic material + 15% inorganic hydroxyapatite** - **Ameloblasts = straited border (ruffled)** - **Final protection**: ameloblasts create a protective covering over the enamel (called the primary cuticle). After this, the ameloblasts eventually die or disappear as the tooth erupts into the mouth. - **Further reduced + falttened** - **Nasmyth's membrane = primary enamel cuticle + reduced enamel epithelium** 1^st^ crystals at enamel-dentine junction -\> grow towards to enamel matrix -\> tuftelin Rooth formation: - Crown complete = inner + outer epithelium cells prolif from cervical loop -\> forms double layer of cells - Root development is guided by a structure called **Hertwig\'s epithelial root sheath (HERS)**, which forms from the **cervical loop** of the enamel organ (where the crown and future root meet). - HERS determines the shape, length, and number of roots by guiding the development of root dentin and surrounding tissues.  **Dentin Formation (Root Dentinogenesis)**: - Cells from the dental papilla located inside the root sheath differentiate into **odontoblasts**, which begin secreting **dentin**. This is similar to the process of dentin formation in the crown but occurs in the root area. - As dentin is deposited, the root starts to grow downward.  **Cementum Formation**: - After some dentin has formed, HERS disintegrates, allowing cells from the surrounding **dental follicle** to migrate and differentiate into **cementoblasts**. - Cementoblasts form a layer of **cementum** on the root's surface, a hard tissue that helps anchor the tooth to the surrounding bone via the periodontal ligament.  **Periodontal Ligament Formation**: - As cementum forms, the surrounding **dental follicle** cells also differentiate into **fibroblasts**, which produce the **periodontal ligament**. This ligament connects the tooth to the alveolar bone, securing it in place.  **Completion**: - Root formation continues even after the tooth erupts into the mouth, with the root gradually lengthening over time. In molars, multiple roots develop through the division of the HERS.  **Cementum Formation**: - **Cementoblasts**, derived from the dental follicle, form a layer of **cementum** over the root surface once **Hertwig\'s epithelial root sheath (HERS)** breaks down. Cementum helps anchor the tooth by providing attachment points for the periodontal ligament.  **Periodontal Ligament (PDL) Formation**: - **Fibroblasts**, also from the dental follicle, begin to produce collagen fibers that form the **periodontal ligament**. This ligament connects the cementum of the tooth root to the **alveolar bone**, acting as a shock absorber and allowing slight tooth movement.  **Alveolar Bone Formation**: - **Osteoblasts** from the dental follicle differentiate and begin forming the **alveolar bone**, which surrounds and supports the tooth socket. This bone forms in response to signals from the developing tooth and PDL, ensuring that the tooth is securely housed in the jaw.  **Gingiva (Gum) Formation**: - The **gingiva** develops from the oral mucosa and forms a protective layer around the neck of the tooth. It helps shield the underlying periodontal tissues from bacteria and trauma. Vascular supply: - Max in bell stage - Clusters found around tooth germ and enters dent papilla in cap stage Nerve supply: - Pioneer nerve fibres approach dev tooth during bud-cap stage - Target dent follicle - Enter pulp only when dentinogenesis starts - Never enter enamel organ  - Detail the role of epithelial-mesenchymal interactions in the induction of developmental processes - Illustrate this with a discussion of the epithelial-ectomesenchymal interactions important in the induction of odontogenesis - Describe the stages classically used to describe the histological progression of tooth development  - Emphasise how a thorough knowledge of normal tooth developments essential to understanding what happens when it goes wrong EMBRYO 6 Anodontia: - Failure of all teeth to dev Hypodontia: - Dev absence of tooth - Norm max laterals, mandib central incisors + 3^rd^ molars - May be associated w alveolar dev - Feature of ectodermal dysplasia -\> hereditary condition w reduced sweat glands, sparse hair - Need radiograph to confirm Oligodontia: - Absence of numerous teeth Hyperdontia: - More teeth than usual - Supernumerary teeth → extra teeth with weird shape - Supplemental teeth → extra teeth w normal morphology - Most common -\> max incisor (mesiodens), max 4^th^ molar, mandib 4^th^ molar (para/distomolar), pre molar - Some fail to erupt and impact - Natal = dev at birth, neonatal = within 30 days of birth Disorders of eruption: Delayed: - Causes misalignment of normal teeth - Root resorption - Interfere w normal eruption - Follicles around unerupted teeth can form dentigerous teeth -\> cysts at crown of dev teeth - Cleidocranial dysotosis, gardners syndrome Impacted: Submerged: Amelogenesis imperfecta: - Bad dev of enamel - Hypoplasia = enamel fails to dev to norm thickness -\> yellow colour + pitted + THIN - Hypomaturation = norm thickness but mottled -\> cloudy white - Hypocalcified = less mineral content Radiographic appearance: - Square shape of crown -\> loss on contour - Thin radiopaque layer of enamel - Low/absent cusps - Hypomaturation = norm enamel thickness but = density as dentin - Hypocalcified = thickness norm but less dense than dentin Dentinogenesis imerfecta: - Hereditary opalescent dentin - Type I = osteogenesis imperfecta - Type II = variable Radio: - Constriction in cervical position - Attrition of occlusal surface - Slender + short roots - Pulp obliteration Dentin dysplasia: - Abnormal dentin formation w abnormal pulp morph - Type 1 = radicular dentin dysplasia - Type 2 = coronal dentin dysplasia Radio: - Short roots and obliterated pulp chamber - Type 2 = large pulp chamber, thistle tube appearance w radiopaque foci Regional odontodysplasia: - Ghost teeth - Enamel + dentine defect -\> hypoplastic + hypocalcified - Failure to erupt Turners hypoplasia: - Infection of prim teeth affecting dev tooth bud of perm teeth - Ill-defined radiolucency Molar incisor hypoplasia: - Thought to be caused by disturbance in dev -\> childhood illness/fever/difficult birth - Chalky teeth, discoloured, crumbly -\> sensitive + painful when brushed **Changes in shape:** Macrodontia: - Tooth big - localised macrodontia Microdontia: - Teeth small - Isolated microdontia common - Most common max lat incisors + wisdom Gemination: - Tooth bud of single tooth tries to divide - Success = norm teeth + numerary tooth - Failure = big ass tooth Fusion: - Fusion of tooth germs Concrescence: - Roots of 2 teeth fuse via cementum Dens invaginatus: - Infolding of outer surface into tooth - Clinically present at incisal edge/cingulum - Diff to clean -\> caries - Thin enamel -\> pulpal disease - On rads -\> circular/oval shape w radiolucent center Dens evaginatus: - Mainly pre-molars -\> Leong's premolar - Outfolding in enamel -\> enamel covered tubercle - Wear + fracture of tubercle -\> pulpal infection Talon cusp: - Anomalous structure - Project lingually from cingulum of incisors - Deep dev groove - Needs to be removed if it interferes w occlusion - Food lodge = RCT - Associated w Rubinstein Tyabi syndrome Accessory cusps: - Cusp of carabelli -\> lingual aspect of max first molar Taurodontism: - Crown of normal shape and size but body is enlarged + short roots - ↑ dist btw CEJ and furcation - Only rads diagnosis - Associated w klinefelters syndrome Dilaceration: - Sharp bend/curce in root/crown - Trauma - Diff extraction - Rounded opaque area w dark shadow in centre in rads if roots bend lingual/buccally Hutchinsons disease: - Congenital syphilis -\> spirochetes affect tooth germ - Screwdriver shaped incisors - Mulberry molars