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CLINICAL EMBRYOLOGY

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CLINICAL EMBRYOLOGY


Introduction

• Growth and development of an individual can be divided into prenatal and the post natal periods.

• The prenatal period of development is a dynamic phase in the development of a human being.

• During this period the height increases by almost 5000 times as compared to only three fold increase during post natal period.


5 principal stages in craniofacial development are

• Germ layer formation and initial organization of craniofacial structures.

• Neural tube formation and initial formation of the oropharynx

• Origins ,migration and interactions of cell population, especially neural crest cells

• Formation of organ system especially the pharyngeal arches and primary and secondary palate

• Final differentiation of tissue .


The prenatal life can be arbitrarily divided into 3 periods

• Period of ovum• Period of embryo• Period of fetus


Period of ovum

• This period extends approx 2 weeks from the time of fertilization.

• During this period the cleavage of the ovum and the attachment of the ovum to the intra uterine wall occurs.


• Human development begins when a sperm fertilizes an oocyte resulting in the formation of zygote.

• The zygote undergoes cleavage, a series of mitotic divisions as it moves along the uterine tube towards the uterus.

• Due to continuous cleavage it turns into a ball of cells when it enters the uterus after 3 days of fertilization, known as morula.


• A fluid filled space develops within the morula, called Blastocele and the entire structure is now known as blasocyst.

• At the end of first week and beginning of second week after the fertilization, blastocyst adheres to the surface of the endometrium and implantation begins and inner cell mass forms a bilaminar disc.


Period of embryo

• This period extends from 14th day to 56th day of intra uterine life.

• During this period the major part of the facial and the cranial region develops.


• Bilaminar disc comprised of epiblast and hypoblast .

• The epiblast is made of columnar cells and separated from cytotrophoblast by a space called amniotic cavity.

• During the 3rd week,gastrulation phase, a narrow trough with slightly bulging sides develops in the midline of the epiblast known as primitive streak.

• During this stage only epiblast cells migrate in the primitive streak and forms all the three germ layers.


• Early in the third week one more important structure develops known as notochord, which is basically formed by the cells in primitive node and pits which proliferate towards cranial end until they reach prechordal plate, which is the future buccopharyngeal membrane.


Neurilation• It is the process of development of the neural

plate, neuroectoderm and finally foldings to produce the neural tube.

• Neural tube is the primordium of the central nervous system.

• The anterior region of the neural tube enlarges to form the forebrain,midbrain,and the hind brain.

• Eight bulges develop in the hind brain known as rhombomeres. Each specific rhombomere give rise to specific neural crest cells which migrate to a specific location.


• Very high levels of ethanol during this period causes deficiency of the midline tissue of the neural plate resulting in maxillary and mandibular deficiency, known as fetal alcohol syndrome.


Role of neural crest cells in the facial development

• Development of the face depends not only on the underlying brain and its subdivisions of prosencephalon,mesencephalon, and rhombencephalon but also on the adjacent secondary neural crest tissue arising from the dorsal margins of the neural folds at a very early stage of embryogenesis.


• Fundamental to facial formation is the differentiation, development and migration of the secondary germ layer tissue designated neural crest ectomesenchyme.

• This transitory pleuripotent tissue arises from the lateral marginal crests of the neural primordium and undergoes an epithelio-mesenchymal transition.


•The neural crest /neural plate is a transient structure which can be subdivided into 4 functional domains.

Cranial neural crest –give rise to various structure of chondrocranium

Trunk neural crest —melanocytes and dorsal root ganglion

Vagal and sacral neural crest ---parasympathetic ganglia of gut

Cardiac neural crest —melanocytes ,neurons and connective

tissue.www.indiandentalacademy.com

• Neural crest cells originating in the mid brain and the from the first two rhombomeres are important in providing mesenchyme needed for development of face ,first pharyngeal arches structure .


• According to Lumsden and Keynes the hindbrain is itself is composed of segments with 8 subunits called as Rhombomeres.

• Neural crest cells destined to 1st branchial arch migrate from the rhombomere 1 and 2 and those for 2 and 3 arches migrate from the rhombomeres 4 and 6,7 respectively.

• Neural crest cells from R8 migrate to 4 and 6 arches.• Most of the cells of R3 and R5 undergo cell death by

apoptosis• The even no. rhombomeres contain exit point for

cranial nerves V,VII and IX which will innervate the branchial arches 1 ,2 and 3.


•During craniofacial development ,neural crest cells especially CNC cells migrate ventrolaterally as they produce the branchial arches.


• Thalidomide and isotretinoin have severe influence on the neural crest migration which lead to various craniofacial malformation.

Clinical significance:-


• Neural crest cells migrating from the rhombomeres express the homeobox (HOX) genes that were expressed in the rhombomeres of origin.


• HOX genes produce transcription factors that bind to the DNA of other genes and regulate the gene expression.

• These genes are important in determining the identity and spatial arrangements of body regions and they also help to determine the pattern and positions of structures developing within the pharyngeal arch.


DNA RNA

TRANSCRIPTION FACTORS

HOMEOBOX GENES

TRNSCRIPTION

+ -

Muscle segment (Msx1,Msx2)

Distalless ( Dlx)

Orthodontical (Otx)

Goosecoid (Gsc)

Sonic hedgehog (Shh)


• The expression of HOX genes are mediated through two main group of regulatory proteins.

• Growth factor family and the steroid/thyroid/retinoic acid super family.


COTROL AT CELLULAR LEVEL

REGULATORY PROTEINS

GROWTH FACTOR FAMILY

e.g. .FGF,EGF,BMPs,TGFalfa

STEROID/THYROID/RETINOIC ACID SUPER FAMIILY

These are the vehicles through which homeobox genes information is expressed in the coordination of cell migration and subsequent cell interactions that regulate the growth.


Neural crest cells form the majority of the facial and cranial skeleton.

However, mesodermal cells also contribute to

the cranium.


http://www.med.unc.edu/embryo_images/unit-hednk/hednk_htms/hednk005.htm

Clinical significance• Mutation in fibroblast growth factor (FGF)

receptor genes are known to affect the suture development in humans and such mutations have been found to occur in Apert and Crouzon syndrome.

• In suture formation the FGF is thought to provide a signal from the duramater preventing the cells from undergoing premature ossification at presumptive sutures and the FGF receptor mutation disrupts these progenitor osteoblast cells to differentiate and causes fusion to occur prematurely.


• Msx-1 and Msx-2 are implicated in craniofacial development and in particular in the initiation, developmental position(Msx-1) and further development(Msx-2) of the tooth buds.

• Bone morphogenetic proteins (BMPs) have been found to have multiple roles not only in bone morphogenesis(BMP-5) but appear to induce dentinogenesis(BMP-7) also.

• The mutation in the Msx gene have been reported to be associated with hypodontia.


Vulnerability of neural crest cells

Deficiency of Superoxide dismutase and catalase enzymes responsible for scavenging free radicals

that damage cells

Exposure of teratogenic compounds such as alcohol and retinoic acid

Cell deathwww.indiandentalacademy.com

Pathogenesis of treacher collins’ syndrome

Excessive cell death in

the trigeminal ganglion

Altered neural crest development

Generalized lack of mesenchymal tissue

Underdevlopment of maxilla and

mandible


Pathogenesis of hemi facial microsomia

Early loss of neural crest cells

Cells migrating to lateral and lower part of the face (longest path) are most affected. these cells are also important in the

formation of great vessels.

Cells migrating to central face tend to

complete their migratory movement

Defect in lower third of the face associated with tetra

logy of Fallot

Midline face defects are rare


Period of the fetus

• This phase extends from 56th day of intra-uterine life till birth.

• In this period ,accelerated growth of the craniofacial structure occurs resulting in an increase in their size as well as change in proportion between the various structure .


Development of the oral structures

• Development of face occurs primarily between 4-8 weeks.

• The growth of the cranial ,facial and oral structures begins around the 21st day after the conception.

• At this stage the embryo is about 3mm in size and head begins to take shape.


• there is progressive increase in the size of the embryonic disc, yet the head and tail end of the disc remain relatively close together.

• This results in the bulging of the disc upward into the amniotic cavity produces two folds known as head and tail folds.


After the formation of

head fold the

developing brain and

the pericardium

form two prominent bulges in

the ventral aspect of

the embryo.www.indiandentalacademy.com

• In between these ,there is a depression called the stomodeum,the floor of which is formed by the buccopharyngeal membrane which separates the stomodeum from the foregut.



http://www.med.unc.edu/embryo_images/unit-hednk/hednk_htms/hednk015a.htm



The buccopharyngeal membrane begins to break down at this stage to allow continuity between pharynx and the stomodeum (primitive oral cavity).


Remnants of the buccopharyngeal membrane are seen between the stomodeum and the pharynx, separating the ectodermally and endodermally covered portions of the first pharyngeal arch.

. Human Age: 29 days View: Dorsal



Early in the fourth week of human development the cranial and cervical (neck) regions make up approximately 1/2 of the embryo's length



The branchial arches

• Differentiation of the face takes place early in the prenatal life, specifically between the 5-7 weeks after the fertilization.

• In the 4th week after the conception, the future face and the neck region located under the forebrain of the future embryo becomes segmented.


• Five branchial arches are formed appearing as rounded, tubular enlargements and are bounded by the clefts and grooves that help in defining each arch.

• Mid and lower facial region develop in part, from the first two, named the mandibular and the hyoid arches.


By the time that the anterior neuropore

closes, the first and second pharyngeal arches are

evident.

. Human Age: 27 days View: Lateral www.indiandentalacademy.com



The first, second, third and fourth arches are visible externally. The sixth arch does not form an external elevation.




The maxillary and mandibular prominences of the first arch contribute the upper and lower jaw. The external ear forms from tissues of the first and second arches. The third and fourth arches form very little of the external surface of the neck, their tissues lying deep in the cervical sinus.

. Human Age: Sixth week View:



The regions between the

pharyngeal arches are termed

pharyngeal clefts. The indentation

just dorsal to the second pharyngeal

cleft is the developing inner ear, the otic pit.

Human Age: 27 days View: Lateral




The clefts that separate the pharyngeal

arches on the external surface of the embryo

are located opposite

pharyngeal pouches

internally.

Human Age: 29 days View: Dorsal



Closing membranes, consisting of

ectoderm, opposed to endoderm,

separate the pharyngeal clefts from

the pouches.




Each arch contains

mesenchyme that is

derived in part from

neural crest and in part

from mesoderm.




The pharyngeal arches are organized

around blood vessels that

extend dorsally from the

developing heart.




illustrates the relationship of the developing heart and aortic sac to the pharyngeal

arches. The arches surround the pharynx and

contain aortic arch blood vessels.

Human Age: 27 days View: Frontal




Nerve supply


The first pharyngeal arch has both a maxillary and a

mandibular prominence. Dorsal to

the first arch is an elevation formed by the underlying trigeminal ganglion, the sensory ganglion for the nerve that supplies tissues derived from the first

arch.Human Age: 29 days View: Lateral




Each of the pharyngeal arches is supplied by a specific cranial nerve.The cells that contribute to the sensory ganglia are derived from neural crest cells and from epibranchial placodes.



Epibranchial placodes are specialized regions of

surface ectoderm, the cells of which invaginate to

contribute to the formation of the sensory ganglia of cranial nerves V, VII, IX, and X.

Human Age: 29 days View: Lateral




Derivatives of the pouches and clefts


Some of the neural crest cells in each of the arches become

cartilage.


Development of the face


• The developing face is initially represented by the frontonasal region, and the first pharyngeal (branchial, visceral) arch.




• The human face is first characterized by an invagination or the dimple in the surface ectoderm layer appearing just below the forebrain.

• As this pit deepens, it forms the outline of the oral cavity and the tissue mass immediately surrounding this oral pit will form the future face.

• In the 4th week the posterior boundary of the oral pit comes into contact with the developing foregut.


• As the oral ectodermal plate meet the endodermal lining of the gut, the membrane disintegrate and the continuity between the oral cavity and the gastrointestinal tract is first gained.

• At 5th week face appear crowded between the rapidly growing forebrain and the heart which occupy most of the chest cavity at this stage.


Soon the mesoderm

covering the developing brain proliferates and

forms a downward projection that

overlaps the upper part of the

stomodeum and this downward

projection is called frontonasal

process



In the inferior and lateral

portion of the frontonasal

process, bilateral localize

area of the surface

ectoderm thickens to form nasal placode



• The growth of the heart affects the development of the face, not only because of the importance of the blood supply to its development but because the face during its early period of rapid growth and organization is crowded between the enlarging forebrain and the pulsating heart.


• Due to migration and proliferation of neural crest cells into the pharyngeal arch the paired structures develop surrounding the stomodeum known as maxillary process and mandibular process

• One of the first events in the formation of facial structures is fusion of medial ends of the mandibular process in the midline to form the chin and the lower lip.


• Medial and lateral nasal process are formed due to proliferation of mesenchyme along the periphery of nasal placode.

• The center of nasal placode becomes thinner due to loss of ectoderm and leads to formation of nasal pits which are the precursors of the nostrils and the nasal cavities.


• Before the fusion of the medial and lateral nasal process the nasal pit undergoes further elongation.

• The raised anterior borders of the nasal pit form the horse shoe shaped structures with the open side below.

• As they grow forward, the inferior ends of the horseshoes come into contact with each other.


• The distance between these two pits remains constant during these period however pit themselves increase in height and length.

• Since the tissue underlying the each nostril represents the first separation of the nasal cavity from the oral cavity, it has been regarded as the primary palate.


• Due to proliferation of underlying mesenchyme in the max.prominences it moves medially toward each other and toward the medial nasal process.

• The medial nasal process of both side also fuse with each other and form intermaxillary segment.


• This segment is important as it gives rise to the philtrum, four incisor teeth, alveolar bone and gingiva surrounding them and primary palate.

• A no of facial prominences fuse between 7 to 10 weeks and give rise to a no. of structures.


• The fusion between the medial nasal process and the maxillary process is a multi step procedure.


•Initially there is contact between the epithelium

covering medial border of max.

process and the lateral border of the medial nasal

process .and form a lamina—known as nasal

fin.



• Upon contact adhesion of two epithelial sheets occur and they become fused into a single sheet.

• Then degeneration of the sheets occurs, resulting in connective tissue penetration through it. and finally formation of upper lip takes place.


• At the posterior limit of the epithelial fin, the epithelial sheets split apart and produces an opening between the nasal pits and roof of the nasal cavity.

• These posterior openings are future internal nares and is the posterior limit of the primary palate.


The medial nasal

prominences merge in the

midline to smooth the

median furrow.



• Later the nasal cavity enlarges posteriorly to form a space overlying the entire oral cavity.

• the oral and nasal cavity are separated by the secondary palatal shelves which are termed “secondary palate” as they are secondary to the primary palate.


Development of tongue


Development of the tongue• The development of the tongue is of

considerable interest because of its importance in functional matrix, its role in epigenetic and environmental influences on the osseous skeleton as well as its role in dental malocclusion.

• Can be studied under following headings• Epithelium• Connective tissue • Muscles


• The tongue arise in the ventral wall of the primitive oropharynx from the inner lining of the first four pharyngeal arches


• During the 4th week of i.u life paired lateral thickenings of mesenchyme appear on the internal aspect of the first pharyngeal arch to form lingual swellings, a centrally located swelling also develops known as Tuberculum impar


• The lingual swelling grow and fuse to form the mucosa of anterior 2/3 of the tongue

• Posterior 1/3 develops from hypo pharyngeal eminence derived from 3 and 4th arch.


• Around the 5th week of i.u life, the ventral aspect of the 2nd 3rd and 4th pharyngeal arches elevate into an united single prominence known as copula which degenerate without significant contribution


• Around the fused lingual swellings there is epithelial proliferation into the underlying mesenchyme takes place. Degeneration of the central cells of this horse shoe shaped lamina forms a sulcus, the liguogingival groove, which frees the body of he tongue from the floor of the mouth except for the midline frenulum of the tongue.



http://www.med.unc.edu/embryo_images/unit-hednk/hednk_htms/hednk025d.htm

The junction of the anterior two-thirds and posterior third of the tongue is at the terminal sulcus. The foramen cecum is the site at which the thyroid gland forms and invaginates.


http://www.med.unc.edu/embryo_images/unit-hednk/hednk_htms/hednk025e.htm

Development of connective tissue and muscle

• Connective tissue develop from local mesenchyme

• Tongue muscle develop from the occipital myotomes and are supplied by hypoglossal nerve

• Taste buds arise by inductive interaction between epithelial cells and invading gustatory nerve cells from the chorda tympani, glossopharyngeal and the vagus nerve. the fungiform papillae are first to be develop at 11 weeks i.u. the circumvallate papillae develop at 2 -5 months i.u.


Development of palate

• The palate begins to develop early in the six week and the process is completed in 12 week.

• The entire palate develops from 2 structure –the primary palate and the secondary palate.

• The primary palate is the triangular shaped part of the palate anterior to the incisive foramen which arises from the fusion of two medial nasal prominences.


The medial nasal prominences contribute the tissues that will form the anterior part of the palate, the primary palate (circled)..



• The secondary palate arises from the paired lateral palatine shelves of the maxilla which are oriented in a superior –inferior plane with the tongue interposed


A frontal cut

illustrates that the

tongue is initially

interposed between

the secondary

palatal shelves.


• Later the lateral palatine shelves of the maxilla become elongated and the tongue becomes relatively smaller and moves inferiorly.


• This allows the shelves to become oriented horizontally to approach one another and to fuse in the midline


• The median palatine raphe is the clinical remnant of fusion between palatine shelves.

• The lateral palatine process also fuses with the nasal septum and the primary palate.

• The fusion between the palatine shelves and the nasal septum proceeds in an antero-posterior direction beginning in the ninth week.


Fusion of the palatal shelves with each other and with the nasal septum separates the nasal cavities from the oval cavity.


Pathogenesis of cleft lip and cleft palate

• This occurs when mesenchymal connective tissue from different embryological structure fail to meet and merge with each other.

• The common form of cleft lip is a result of failure of fusion of the median nasal process with the max process.

• It may be unilateral or bilateral and may extends into the alveolar process.


• Cleft palate is the result of failure of the lateral palatine process to fuse with each other ,with the nasal septum or with the primary palate.


• Even at this early stage the growth pattern of the face is downward and forward as it grows out from between these two organs.

• Important related occurrences are the flexures that occur during the 4th week in the region of the future neck.

• The brain flexes ventrally, then dorsally and as a result the head becomes more erect.

Further growth of the face:--


Development of the skull

• The skull is formed by mesenchymal connective tissue around the developing brain.


• The development of the skull is considered in two components-

Neurocranium-calvaria and base of the skull and derived from occipital somites.

Viscerocranium-skeleton of face and other associated structures

Derived from neural crest ectoderm.

Each component has some structure that form by endochondral ossification (cartilaginous component) and other structures that form by intramembranous ossification (membranous component) .


Cartilaginous neurocranium

• Consists of several cartilages that fuse and undergo endochondral ossification to give rise to base of the skull.

• The cartilaginous junction between two bones are called synchondroses.

• The new cartilage cells continually form in the center of the synchondroses,move peripherally and then undergo endochondral ossification along the lateral margins.


The bone formed by this process are

• Occipital bone• Body of the sphenoid bone• Ethmoid bone• Vomer• Petrous and mastoid part of the temporal

bone.


Membranous neurocranium

• These arises by the intramembranous ossification of the mesenchyme around the developing brain.

• Sutures (syndesmoses) are uncalcified dense sheets of connective tissue that separate the bones of the calvaria.

• These sutures are also derived from two sources-neural crest cells (sagittal suture) and paraxial mesoderm (coronal suture).

• When sutures come together they form a region of dense connective tissue known as FONTANELLES.

• They help the calvaria to change the shape during birth by a process called MOLDING.


The bones formed by this process are

• Flat bones of calvaria.• Superior portion of the frontal ,occipital

and parietal bones.


viscerocranium• Includes the facial skeleton arises from the

pharyngeal arches.

Cartilaginous component -includes middle ear ossicles,the styloid process of temporal bone,the hyoid bone and the laryngeal cartlilages.

Membranous viscerocranium —includes maxilla ,zygomatic bone, the squamous temporal bone and the mandible. except for the mand condyle,and the midline of the chin.


Development of mandible and TMJ

• The template for the mandible is laid down by meckle’s cartilage of the first pharyngeal arch.

• Initial intramembranous ossification occurs at 6 week post conception, the earliest of bones to ossify.

• The primary ossification center is located at the side of bifurcation of the inferior alveolar nerve into the incisive and the mental nerve.

• Then it spreads anteroposteriorly on the lateral aspect of the meckle’s cartilage to encompass the cartilage which later disintegrates.


• Secondary cartilage develops at the site of coronoid and condylar process and at the angle.

• By 11 weeks secondary cartilage has developed, forming the condylar head which is separated from the temporal bone by a fibrous connective tissue. and commencement of ossification of this cartilage takes place at 18-19 weeks.

• The cartilaginous head of the condyle enveloped in the fibrous covering that is continuous with the joint capsule, persists and function as a growth center until about the 25 year of post natal life.

• Each half of the mandible develops as a single skeletal system in which meckle's cartilage serves as an initial template but does not contribute directly to the formation of mandible.


9 weeks 16 weeks

24 weeks 30 weeks


• As the two halves of the mandible continue to grow fibrous connective tissue known as symphyseal cartilage unite the two halves of the mandible and serve as a growth site until the first year after birth by which time it is calcified.

• The angle of the mandible at birth is about 130 degree with the condyle,thus nearly in the line with the body.

• Later all these cartilages, together with the ventral most tip of the meckle’s cartilage, ossify endochondrally to conjoin with the membranous bone of the body of the mandible.


• Forward growthDeposition of new bone along the

anterior surface of the mandible

Backward growth

Accretion along the post. border of the

ramus extending from condyle to the angle of

the mandible.

heightDevelopment of the

dentition and the alv.bone.


Development of maxilla

• A primary intramembranous ossification center appear for each maxilla in the 8th week IU at the termination of infraorbital nerve just above the canine tooth dental lamina.

• two further itramembranous premaxillary centers appear anteriorly on each side in the 8th week and rapidly fuse with the primary maxillary center.


Prenatal changing relationship between maxilla and mandible

• During intra uterine development, the relative size of the maxilla and the mandible vary widely.

• Initially the mandible is considerably larger than the maxilla, a predominance later diminished by the relatively greater development of the maxilla, changing the jaw relationship from angle class III to class II.


• At about 8 weeks post conception, the maxilla overlaps the mandible. subsequently the mandible grows more rapidly, equaling the maxilla by 11 weeks post conception.

• Mandibular growth then lags between the 13th to 20th weeks, due to a change over from MECKLE’S cartilage to the condylar secondary cartilage as the main growth center of the mandible.

• At birth the mandible is generally retrognathic to the maxilla ,although the two may be of equal size.


Clinical significance•Fibroblast growth factor (FGFs) and fibroblast growth factor receptors (FGFRs) play a important role in the skeletal dysplasia by controlling the cellular events such as proliferation ,differentiation, and migration.•FGFR-1 and FGFR-2 are expressed in prebone and precartilage regions including craniofacial structure.•FGFR-3 is expressed in cartilage growth plates of long bones.


FGFR-1

FGFR-2

FGFR-3

Osteogenic differentiation

+ proliferation

Unclear role

craniosynostosis

mutation

dwarfism

+


• Crnioschisis (anencephaly) crniosynostosis

plagiocephalyacrocephaly scaphocephalywww.indiandentalacademy.com

The fetal period—3—9 month

• Craniofacial changes—by the 3rd month face assumes more human appearance.

• During the fetal period the head increases in length from approx. 12 to 74mm and height from 20 to 100mm thus maintaining a fairly constant ratio of width to length but not to the height.

• Prior to 5th month the height increase is greatest where as length and width increases are proportional.


• At birth the cranial vault is approx.8times larger than the face.

• In the embryonic period the cranium to face ratio may be as high as 40:1 dropping at 4 months to 5:1 because of the differentially more rapid facial growth during this period.

• The cranium then grows faster in the late prenatal months to attain 8:1 ratio at birth. which again changes to 2:1 in adults due to post natal facial growth.

• At the same time the no of skeletal bones is reduced from 45 separate bones at birth to 22 in adult.


Development of teeth• By the 7th week, the epithelial labial lamina

develops on the perimeter of the max. and the mand. process .

• This wedge of epithelial cells penetrates the underlying connective tissue to separate the tissue of future alveolar ridge from the lip.

• At the same time a second lamina lingual to the labial lamina appears and grows into the alveolar ridge.—known as dental lamina which at regular intervals will give rise to enamel organ which will ultimately develop into tooth.


Molecular regulation of tooth development

• Tooth development represents a classic example of epithelium and neural crest derived mesenchymal interaction.

• Bud stage---regulation center —bud epithelium• Cap and bell stage (enamel knot)-- regulation

center –mesenchyme• BMPs,FGFs ,sonichedgehog,MSX1and 2

interact in complex pathway to produce cell differentiation and patterning for each tooth.


Development of the salivary gland

• All three major glands develop during 6—8 weeks due to proliferation of the oral mucosa epithelium into the underlying mesenchyme.

• The connective tissue around the developing glands forms the capsule as well as grow into the glands to subdivide them into the lobules.

• The acini of the mucous gland become functional during the 6th week where as serous gland become functional by birth,


conclusion• The clinician’s requirement of the anticipated endpoint of

growth and development of the face to determine whether orthosurgical intervention is desirable is one of the great challenges with which developmental biologists are confronted.

• The hope of biomimetic intervention by genetic engineering and molecular factors signaling utilization in controlling growth, once considered only a remote possibility is now becoming ever more realistic.

• With the increasing identification of growth factors ,genes, and chromosomes responsible for the development of the face orthodontists are now in a better position to advise patterns of the ultimate outcome of prognosis of various dentofacial malformation and malocclusions of their progeny.


References:---

• Geoffry H.Sperber—New insights in facial development—Seminar in orthodontics,March 2006,vol-12,no-1,page,4-10.

• Vinod Krishnan----Neural crest cells,homeobox genes and craniofacial development----J Ind Orthod Soc 2002,35,page no.42—50.

• Cobourne M.T---Construction for the modern head—current concepts in craniofacial development—J of Orthod,2000,vol-27,page,307-314.


• Vinod Krishnan---Genomics and orofacial clefts--J Ind Orthod Soc 2003,vol--36,page no.39—51.

• Graham A ,Okabe M et al—the role of the endoderm in the development and evolution of the pharyngeal arches— Journal of Anatomy-2005,vol-207,page,479-487.

• Helms JA, Cordero D et al—New insights into craniofacial morphogenesis—Development,2005,vol-132,page,851-861.


• Tapadia MD,Cordero DR et al—It’s all in your head;new insights into craniofacial development and deformation-- Journal of Anatomy-2005,vol-207,page,461-477.

• Radlanski RJ et al—Bone remodelling of the human mandible during prenatal development—J Orofacial Orthop ,2001,vol-62, page ,191-201.

• Trenouth MJ—Changes in the jaw relationships during human foetal cranio-facial growth-Br J Orthod 1985,vol-12, page,33-39.


• Williams R.Proffit----Contemporary orthodontics—3rd edition.St.Louis,CV Mosby,2005.page.63-93.

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• Samara E.Bishara---Textbook of Orthodontics—WB Saunders,2003

• Thesleff I ,Sharpe P— Signaling networks regulating dental development-Mech Dev.1997,vol-67,page 111


• P.A.Mossey —The heritability of malocclusion.part-1---Genetics principles and terminology—BJO 1999 June,vol.26,page.103—113.

• Kalevi Koski et al—cranial growth centers; facts or fallacies?—Am J Orthod.1968Aug-Page-566-583

• Bernard G.Sarnat---growth pattern of the mandible: some reflections-- Am J Orthod.1986,Sep,vol-90.Page-221—233.

• Irma Thesleff—Homeobox genes and growth factors in regulation of craniofacial and tooth morphogenesis—Acta Odontol Scand,1995vol.53,page,129-134.


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