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INTRODUCTION
Embryology:- Study of development of an individual before birth. Why a medical student should study embryology???

This subject tells how the organs of the body develop. It helps us to understand many complicated facts of adult anatomy. understand abnormal growth & To development it is very much essential to know the normal pattern of growth & development.

DEFINITIONS
Growth: Self multiplication of living substances (J.S.HUXLEY) - An increase in size(TODD) - Increase in size, change in proportion & progressive complexity (KROGMAN) - Change in any morphologic parameter which is measurable (MOSS) Development: Progress towards maturity (TODD)

TERMINOLOGY & ABBREVATIONS STOMATODEUM: It is the future mouth. It is a depression bounded cranially by a bulging produced by the brain & caudually by a bulging produced by the pericardial cavity. NP- Nasal Process. MNP-Medial Nasal Process. LNP Lateral Nasal Process. MP Maxillary Prominences. E.O Enamel Organ

DEVELOPMENT OF FACE

Begins at 4th week with the facial prominences consisting primarily of neural crest derived mesenchyme & formed mainly by the 1st pair of pharygeal arches. The maxillary prominences can be seen lateral to the stomatodeum & Mandibular prominences caudal to it. Fronto nasal prominence formed by proliferation of mesenchyme ventral to brain vesicles, constitute the upper border of stomatodeum. On both sides of the FNP, local thickneings of surface ectoderm, the nasal (or) olfactory placodes are seen under inductive influence of fore brain.

 During 5th week: - Nasal placodes invaginate to form nasal pits

thereby creating a ridge of tissue around each pit, the nasal prominence(NP). - Outer edge of NP is lateral nasal Prominence & inner edge is Medial nasal prominence.

 During 6th & 7th Weeks: - Maxillary prominences increase in size growing

medially, compressing the MNP towards the midline. As a result, they fuse. Hence, the upper lip is formed by two MNP & two MP. - LNP does not participate in the formation of upper lip. - Mandibular prominence forms the jaws & lower lip that merge across the midline. - MP & LNP are separated by a deep furrow, the nasolacrimal groove. - Ectoderm in the floor of this groove forms a solid epithelial cord which forms nasolacrimal duct; its upper end widens to form the lacrimal sac.

- The MP enlarge to form cheek and maxillae.

- Nose is formed from 5 facial prominences which are: - Bridge from frontal prominence. - crest & tip from merged MNP. - Alae from LNP.

DEVELOPMENT OF NOSE

- During 6th week the nasal pits deepen considerably, partly because of growth of surrounding NP & partly because of their penetration into the underlying mesenchyme. - Nose receives contributions from: . Nasal septum FNP . Medial nasal process . Alae LNP -

DEVELOPMENT OF PARANASAL SINUSES

Para nasal Sinuses develop as diverticula of the lateral nasal walls & extend into corresponding bones.

CHEEKS:

After formation of upper & lower lips, the maxillary & mandibular process undergo progressive fusion with each other to form cheeks.

EYES: . Region of eye is first seen as an ectodermal thickening the lens placode, which appears on ventral lateral side of developing forebrain, lateral & cranial to nasal placode.

. The placode sinks below the surface & is eventually cut off from surface ectoderm. . The developing eyeballs produces a bulging which are first directed laterally & lie in the angles b/w MP & LNP. . With the narrowing of FNP they come to face forwards. . The eyelids are derived from folds of ectoderm that are formed above & below the eyes & by mesoderm enclosed with in the folds.

MOLECULAR REGULATION OF FACIAL DEVELOPMENT

Much of face is derived from neural crest cells that migrate into pharyngeal arches from the edges of cranial neural fold. In the hind brain, these cells originate from segmented regions known as RHOMBOMERES. There are eight of these segments (R1-R8).

 Crest cells from specific segments populate specific arches. - Midbrain + R1,R2 1st arch R4 2nd arch R6,R7 3rd arch R8 4th & 6th arches

 Patterning of pharyngeal arches appears to be regulated by HOX GENES which are carried to arches by migrating neural crest cells. Retinoids (Retinoic Acid) can also regulate HOX gene expression in a concentration dependent manner through RARES. In addition to the HOX genes, OTX2 may precipitate in morphogenesis of 1st arch.

PHARYNGEAL ARCHES
- Each arch consists of a core of mesenchymal tissue covered on the outside by surface ectoderm & on the inside by epithelium of endodermal origin. - In addition, they also contain neural crest cells which contribute to skeletal components of face. - Mesoderm gives rise to musculature of face & neck. - Each arch has 3 components: Muscular, Nerve, Arterial

DEVELOPMENT OF TONGUE
Appears at approximately 4 weeks in the form of 2 lateral lingual swellings & 1 medial swelling, the tuberculum impar. These 3 originate from 1st arch. . A second median swelling, copula (or) hypobranchial eminence is formed by mesoderm of 2,3 & 4 arches. .

As lateral swellings increases in size, they overgrow tuberculum impar forming anterior 2/3 of tongue. . Posterior 1/3 develops from 2,3,& part of 4th arches with 3rd arch burying the 2nd arch. . Muscles of tongue develop from occipital somites/myotomes.

OVER ALL DEVELOPMENT OF TONGUE

 CLINICAL CORRELATION & ANOMALIES: Ankyloglossia Macroglossia Microglossia Fissured tongue Aglossia Bifid tongue

DEVELOPMENT OF PALATE
INTERMAXILLARY SEGMENT: - formed due to merging of two medial nasal prominences - Composed of a. Labial component forms philtrum of upper lip. b. Upper Jaw component carries the 4 incisor c. Palatal component forms triangular primary palate. It is continous with nasal septum.

 SECONDARY PALATE:

. Formed by 2 shelf like outgrowths from the MP, the palatine shelves which appear in the 6th week of development. Directed obliquely on each side of tongue. . In the 7th week, the palatine shelves ascend horizontally above the tongue, fuse & form secondary palate. . Anteriorly it fuses with primary palate where incisive foramen is present.

 CLINICAL CORRELATION & ANOMALIES: - Facial Clefts: Cleft Lip Cleft Palate - Oblique facial clefts failure of MP to merge with LNP. - Median cleft Lip Rare incomplete merging of the two MNP in the midline. - Teratogens are likely to cause cleft lip defects if the embryo is exposed to them during 5th & 6th weeks. - The palate is most susceptible b/w 7th & 8th weeks.

 DEVELOPMENTAL ANOMALIES OF FACE: - Macrostomia - Microstomia - Bifid Nose - Proboscis - Cyclops - Macro & Micro gnathia - Hyperptelorism - Lips with congenital pits or double lip - Entire 1st arch may be underdeveloped on one or both sides - MANDIBULO FACIAL DYSOSTOSIS

TERATOLOGY
Also known as embryopathy. Defined as the pathology of the unborn. Physical factors like radiation from Xray or radium produces skull defects, cleft palate.

CHEMICAL AGENTS
AMINOPTERIN- An antimetabolite & antagonist of folic acid used to induce abortion. If this fails the child shows encephaly, hydrocephalus, hare-lip or cleft palate. DIPHENYL HYDANTOIN Craniofacial defects

 DIAZEPAM (VALIUM) Cleft lip with or without cleft palate. TETRACYCLINES Tooth anomalies ALCOHOL Short palpebral fissures & hypoplasia of maxilla. CORTISONE In early pregnancy causes cleft palate.

SYNDROMES ASSOCIATED WITH DEVELOPMENTAL DEFECTS OF FACE

GOLDENHAR SYNDROME PIERRE ROBIN SYNDROME PARRY ROMBERG SYNDROME VANDER WOUDES SYNDROME MELKERSON ROSENTHAL SYNDROME DOWNS SYNDROME BECKWITH WIEDE MANN SYNDROME RUBENSTEIN- TAYBI SYNDROME KLINEFELTERS SYNDROME

DEVELOPMENT OF TOOTH
Starts at around 6 weeks of development with the continouous band of thickened epithelium ( primary epithelial band) Roughly horse shoe shaped. Primary epithelial band - Vestibular lamina - Dental lamina

. The downgrowths from the dental lamina represents the beginning of the enamelorgan of the tooth bud of a deciduous tooth. . As cell proliforation continues the enamel organ increase in size & changes in shape. . The stages of tooth development correlates with the shape of the enamel organ.

BUDSTAGE
The enamel organ consists of peripherally located low columnar cells & centrally located polygonal cells. Cells of the tooth bud& surrounding mesenchyme undergo mitosis. The Neural crest cells migrate to the area & the ectomesenchyme surrounding the developing tooth bud condense. Ectomesenchyme subjacent to enamel organ is dental papilla. Ectomesenchyme surrounding E.O & dental

CAP STAGE
Characterised by shallow invagination on the deep surface. Peripheral cuboidal cells covering the convexity OEE Tall, columnar cells in the concavity represent IEE. The third layer stellate reticulum is also seen in this stage in the centre of E.O Temporary Structures enamel knot & enamel chord are seen with act as reservior of dividing cells for the growing E.O

 Divided into early & advanced stages. In addition to OEE,IEE & St.reticulum another layer STRATUM INTERMEDIUM is seen present between IEE & St.Reticulum this layer is essential for enamel formation. S.R collapses before enamel formation begins, reducing the distance between the centrally situated ameloblasts & the nutrients capillaries. Membrana preformativa is the basement membrane that separates E.O & Dental papilla.

BELL STAGE

ADVANCE BELL

Boundary between IEE & odontoblasts outlines the future DEJ. Cervical portion of the E.O gives rise to the Hertwigs epithelial root sheath.

DEVELOPMENTAL DISTURBANCES OF TEETH

DISTURBANCES IN SIZE: - Microdontia - Macrodontia . DISTURBANCES IN NUMBER: - Anodontia - Oligodontia - Supernumerary Teeth

DISTURBANCES IN STRUCTURE: - Amelogenesis Imperfecta - Dentinogenesis Imperfecta

 DISTURBANCES IN SHAPE: - Gemination - Fusion - Concrescence - Dilaceration - Talon cusp - Dens In Dente - Dens Evaginatus - Taurodontisn

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