GENERAL EMBRYOLOGY

Presented byDr. Sharmin Sultana

BDS, FCPS Part II TraineeDept of Orthodontics and Dentofacial

OrthopedicsDhaka Dental College and Hospital

GENERAL EMBRYOLOGY

Germ Cell Formation and FertilizationHumans have approxi- mately 23,000 genes on 46 chromosomes. In somatic cells, chromosomes appear as 23 homologous pairs to form the diploid number of 46 chromosome. There are 22 pairs of matching chromosomes, the autosomes, and one pair of sex chromosomes. If the sex pair is XX, the individual is genetically female; if the pair is XY, the individual is genetically male. One chromosome of each pair is derived from the maternal gamete, the oocyte, and one from the paternal gamete, the sperm. Thus, each gamete contains a haploid number of 23 chromosomes, and the unión of the gametes at fertilization restores the diploid number of 46. The process that produces germ cells with half the number of chromosomes of the somatic cell is called meiosis.

MITOSIS: Before mitotic cell division begins, DNA is first replicated during the S (synthetic) phase of the cell cycle so that the amount of DNA is doubled to a value known as tetraploid (which is 4 times the amount of DNA found in the germ cell). During mitosis the chromosomes containing this tetraploid amount of DNA are split and distributed equally between the two resulting cells; thus both cells have a diploid DNA quantity and chromosome number, which duplicates the parent cell exactly.

Meiosis: involve two sets of cell division.

DNA is replicated to the tetraploid value Homologous chromosomes approach each other. so that homologous chromosomes pair, and each member of the pair consists of two chromatids.

Intimately paired homologous chromosomes interchange chromatid fragments [crossover]. By formation X like structure the chiasma.

Double-structured chromosomes pull apart.

Anaphase of the first meiotic división.

homologus pairs then separate into two daughter cells. In the first division the number of chromosomes is halved, and each daughter cell contains a diploid amount of DNA quantity chromosome number.

During the second meiotic división, the double-structured chromosomes split at the centromere. completion of división, each of the four daughter cell, each gamet contain 23 single (haploid number) chromosomes and haploid amount of DNA, each cells are different from each other.

Birth defect : Chromosomal and Genetic Factors Abnormalities in chromosome number may originate during meiotic or mitotic division.The process occasionally malfunctions, producing zygotes with an abnormal number of chromosomes and individuals with congenital defects that sometimes affect the mouth and teeth. For example, an abnormal number of chromosomes can result from the failure of a homologous chromosome pair to separate during meiosis,sometimes however separation does not occur (nondisjunction), and both member of a pair move into one cell. so that the daughter cells contain 24 or 22 chromosomes. If, on fertilization, a gamete containing 24 chromosomes fuses with a normal gamete (containing 23), the resulting zygote will possess 47 chromosomes; or 45 chromosome one homologous pair has a third component. Thus the cells are trisomic for a given pair of chromosomes. If one member of the homologous chromosome pair is missing, a rare condition known as monosomy prevails.

The best known example of trisomy is Down syndrome, or trisomy 21. Among features of Down syndrome are growth retardation, mental retardation, craniofacial abnormalities like-facial clefts, a shortened palate, a protruding and

fissured tongue, and delayed eruption of teeth and hypodontia. Also have upward slantíng eyes, epícantlial folds (extra skin folds at the

medial corners of the eyes], fíat facies, and small ears; cardiac defects. These individuáis aiso have an increased chance of deveioping ieukemia,

infections, thyroid dysfunction, and premature aging. Furthermore, an increased frequency and earlier onset of Aizheimer disease is observed among persons with Down syndrome.

Trisomy 13The main abnormalities of trisomy 13 are intellectual dísability, holoprosencephaly, congenital heart defects, deafness, cleft lip and palate, and eye defects, such as microphthal- mia. anophthalmia, and coloboma.The incidente of this abnormality is approximately 1 in 20,000 live births, and more than 90% of the infants die in the first month after birth. Approximately 5% live beyond 1 year.

TURNER Syndrome Turner syndrome, with a 45, X karyotype, Is the oniy monosomy compatible with life. Even then, 98% of all fetuses with the syndrome are spontaneously aborted. The few

that survive are unmistakably female in appearance and are characterized by the absence of ovaries (gonadal dysgenesis) and short stature.

Other common associated abnormalities are webbed neck, lymphedema of the extremities, skeletal deformities, and a broad chest with widely spaced nipples.

Approximately 10% of all human malformations are caused by an alteration in a single gene. Such alterations are transmitted in several ways, of which two are of special importance. First, if the malformation results from autosomal dominant inheritance, the affected gene generally is inherited from only one parent. The trait usually appears in every generation and can be transmitted by the affected parent to statistically half of the children.

Examples of autosomal dominant conditions include- achondroplasia, cleidocranial dysostosis, Cherubism, osteogenesis imperfecta, dentinogenesis imperfect and some forms of amelogenesis imperfecta; the latter two conditions result in abnormal formation of the dental hard tissues.

Second, when the malformation is due to autosomal recessive inheritance, the abnormal gene can express itself only when it is received from both parents. Examples include chondroectodermal dysplasia, some cases of microcephaly, and cystic fibrosis.

ACHONDROPLASIA A common type of genetic dwarfism Failure of proliferation of cartilage in epiphyses and base of skull Short limbs but normal sized skull Middle third of face retrusive due to deficient growth of skull base, profile to be concave. The mandible often protrusive Usually severe malocclusion

Cleidocranial Dysostosis Rare genetic disorder causing defective formation of clavicles Delayed closure of fontanelles and other defects Many permanent teeth typically remain embedded in the jaw Many additional unerupted teeth also present Sometimes many dentigerous cysts

Cherubism Inherited as autosomal dominant

trait Jaw swellings appear in infancy Angle regions of mandible affected

symmetrically giving chubby face Symmetrical involvement of maxilla

also in more severe cases Teeth are frequently displaced and

maybe loosened Radiographically, lesions appear as

multilocular cyst like areas

Amelogenesis imperfecta Inheritance can be autosomal dominant, recessive or x- linked. However, the most

common types have an autosomal inheritance and are thought to be caused by mutations in the AMEL-X gene, which codes for ameloblastin (C4), enamelin (C4) or tuftelin (C1). In the case of autosomal dominant type of amelogenesis imperfect, the locus of the defective gene is on chromosome 4q 21 to which enamelin maps.

1. Hypoplastic amelogenesis imperfecta Enamel is randomly pitted, grooved, or very thin Enamel is hard and translucent Stained Teeth are not especially susceptible to caries

2. Hypomaturation amelogenesis imperfecta The enamel is normal in form Opaque, white to brownish-yellow Mottled fluoride effects Soft and vulnerable to attrition

3. Hypocalcified amelogenesis imperfect Enamel form in normal quantity but poorly calcified Normal in thickness, but weak and opaque or chalky appearance Teeth tend to stain Relatively rapid worn away Incisors may acquire a shouldered form

Dentinogenesis Imperfecta Dentine is soft Tooth discoloration and attrition is less severe in permanent teeth Class III malocclusion is associated in over 70% Dental development delayed in 20%

Osteogenesis imperfect ( brittle bone syndrome) The fragile bones due to inadequate type I collagen foemation Multiple fractures typically lead to gross deformities Variable degrees of dentinogenesis imperfecta associated type III and Iv

FORMATION OF THE THREE-LAYERED EMBRYO After fertilization, mammalian development involves a phase of rapid proliferation and

migration of cells, little or no differentiation. This proliferative phase lasts until three germ layers have formed. In summary, the fertilized egg initially undergoes a series of rapid divisions that lead

to the formation of a ball of cells called the MORULA.

Formation of the three-layered embryo cont…..

Morula Fluid seeps into the morula cells realign themselves to form a fluid-filled hollow ball, called blastocyst Two cell populations now can be distinguished within the blastocyst: those lining the cavity (the primary yolk sac), called trophooblast cells and a small cluster within the cavity, called the inner cell mass or embryoblast .

The embryoblast cells form the embryo proper, whereas the trophoblast cells are associated with implantation of the embryo and formation of the placenta;

Formation of the three-layered embryo cont…..

At about day 8 of gestation, the cells of the embryoblast differentiate into a two-layered disk, called the bilaminar germ disk.

The cells situated dorsally, or ectodermal layer, are columnar and reorganize to form the amniotic cavity.

Those on the ventral aspect, the endodermallayer, are cuboidal and form the roof of a second cavity (the secondary yolk sac), which develops from the migration of peripheral cells of the extra embryonic endodermal layer.

This configuration is completed after 2 weeks of development. During that time the axis of the embryo is established and is represented by a slight enlargement of the ectodermal and endodermal cells at the head (or rostral) end of the embryo in a region known as the prochordal plate.

Formation of the three-layered embryo cont…..

During the third week of development the bilaminar embryonic disk is converted to a trilaminar disk. the floor of the amniotic cavity is formed by ectoderm, and within it a structure called the primitive streak develops along the midline.

This structure is a narrow groove with slightly bulging areas on each side. The rostral end of the streak finishes in a small depression called the primitive node, or pit. Cells of the ectodermal layer divide at the node and migrate between the ectoderm and endoderm to form a solid column that pushes forward in the midline as far as the prochordal plate. Through canalization of this cord of cells, the notochord is formed to support the primitive embryo.

Elsewhere alongside the primitive streak, cells of the ectodermal layer divide and migrate toward the streak, where they invaginate and spread laterally between the ectoderm and endoderm. These cells, sometimes called the mesoblast, infiltrate and push away the extraembryonic endodermal cells of the hypoblast, except for the prochordal plate, to form the true embryonic endoderm.

They also pack the space between the newly formed embryonic endoderm and the ectoderm to form a third layer of cells, the mesoderm . In addition to spreading laterally, cells spread progressively forward, passing on each side of the notochord and prochordal plate. The cells that accumulate anterior to the prochordal plate as a result of this migration give rise to the cardiac plate, the structure in which the heart forms. As a result of these cell migrations, the notochord and mesoderm now completely separate the ectoderm from the endoderm , except in the region of the prochordal plate and in a similar area of fusion at the tail (caudal) end of the embryo, the cloacal plate.

Derivatives of the germ layers and neural crest.

Neural Crest Derivatives

1. Cranial nerve ganglia.2. Spinal [dorsal root] ganglia 3. Sympathetic chain and preaortic ganglia 4. Parasympathetic ganglia of the gastrointestinal tract 5. Meninges [forebrain], arachnoid meter and pia meter, duremetter, leptomeninges.6. Schwann cells 7. Glial cells8. Connective tissue and bones of the face and skull9. Dermis in face and neck10. Melanocytes11. Smooth muscle cells to blood vessels of the face and forebrain12. Odontobiasts (dentin), cement, pulp, alveolar bone, and periodontal ligament.13. C cells of the thyroid gland 14. Conotruncal septum in the heart 15. Adrenal medulla

Neural Crest Cell Problems As the neural tube forms, a group of cells separate from the neuroectoderm. These cells have the capacity to migrate and differentiate extensively within the

developing embryo, and they are the basis for structures such as the spinal sensory ganglia, sympathetic neurons, Schwann cells, pigment cells, and meninges. In the avian embryo these cells can be distinguished differentiating and separating at the crest of the neural folds, hence the name neural crest cells.

Neural crest cells in the head region have an important role. In addition to assisting in the formation of the cranial sensory ganglia, they also differentiate to form most of the connective tissue of the head.

Embryonic connective tissue elsewhere is derived from mesoderm and is known as mesenchyme, whereas in the head it is known as ectomesenchyme, reflecting its origin from neuroectoderm.

In a dental context the proper migration of neural crest cells is essential for the development of the face and the teeth. All the tissues of the tooth(except enamel and perhaps some cementum) and its supporting apparatus are derived directly from neural crest cells, and their depletion prevents proper dental development.

Neural Crest Cell Problems cont….. At the completion of the miqration of the neural crest cells in the fourth week of human

embryonic life, they form practically all of the loose mesenchymal tissue in the facial region that lies between the surface ectoderm and the underlying forebrain and eye and most of the mesenchyme in the mandibular arch. Most of the neural crest cells in the facial area later differentiate into skeletal and connective tissues, including the bones of the jaw and the teeth.

The importance of neural crest migration and the possibility of drug-induced impairment has been demonstrated clearly by unfortunate experience.In the 1960s and 70s, exposure to thalidomide caused major congenital defects including facial anomalies in thousands of children. In the 1980s, severe facial malformations related to the anti-acne drug isotretinoin (Accutane) were reported. The similarities in the defects make it likely that both these drugs affect the

formation and/or migration of neural crest cells.

Mandibulofacial dysostosis (Treacher Collins syndrome)

Altered neural crest development also has been implicated in mandibulofacial dysostosis (Treacher Collins syndrome) . In Treacher Collins syndrome, both the maxilla and mandible are underdeveloped as a result

of a generalized lack of mesenchymal tissue. Enlarged tongue, possible cleft palate. Lack of middle ear development which results in loss of hearing. The best evidence suggests that the problem arises because of excessive cell death (cause

unknown) in the trigeminal ganglion, which secondarily affects neural crest-derived cells.

Pierre Robin syndrome extremely small mandible at birth. usually accompanied by a cleft palate because the

restriction on displacement of the mandible forces the tongue upward and prevents normal closure of the palatal shelves.

The reduced volume of the oral cavity can lead to respiratory difficulty at birth, and it may be necessary to perform a tracheostomy so the infant can breathe.

Early mandibular advancement via distraction osteogenesis has been used recently in these severely affected infants to provide more space for an airway so that the tracheostomy can be closed.

It has been estimated that about one-third of the Pierre Robin patients have a defect in cartilage formation and can be said to have Stickler syndrome. Not surprisingly, this group have limited growth potential. Catch-up growth is most likely when the original problem was mechanical growth restriction that no longer existed after birth.

Neural Crest Cell Problems cont…..Hemifacial microsomia Hemifacial microsomia, as the name suggests,

is primarily a unilateral and always an asymmetrical problem.

It is characterized by a lack of tissue on the affected side of the face.

Typically, the external ear is deformed and both the ramus of the mandible and associated soft tissues (muscle, fascia) are deficient or missing.

An early explanation of the condition was that it was due to hemorrhage from the stapedial artery at the time, about 6 weeks after conception, when the ma-xillary artery takes over the blood supply to the affected area.

More recent work suggests that, although hemorrhage at the critical time may be involved, hemifacial microsomia arises primarily from early loss of neural crest cell.

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To be continued………..