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EMBRYOLOGY OF THE FACE INTRODUCTION Human being comes into existence as single fertilized ovum cell. Fertilization involves the fusion of the male and female gem cells (i.e. Spermatozoa and Ova) to form a Zygote, which commences the formation of a new individual. Prenatal development occupies 10-lunar months. Pre-natal development is divided into 3 successive phases. The 1st 2 phases can be combined to constitute the Embryonic stage of development. The 3rd phase is called the fetal stage. The forming individual can be described as an Embryo or Fetus depending on its developmental stage.

1ST phase begins at fertilization and spans the first 4 weeks of the development. This phase involves largely cellular proliferation and migration with some differentiation of cell populations. Few congenital defects can result from this period of development because, if the disturbance is severe, the embryo is lost but if it is less severe the proliferative response can compensate by a process of cell renewal. The second phase spans the next 4 weeks of development and it is largely characterized by the differentiation of all major external and internal structures (morphogenesis). This is a particularly vulnerable period of development for the

embryo because it involves many intricate embryologic processes and it is during this period that many recognized congenital defects develop. From the end of the second phase to third, further development is largely a matter of growth and maturation and the embryo is now called fetus. INDUCTION, COMPETENCE AND DIFFERENTIATION These terms, induction, competence and differentiation, describe important concepts in Embryology. All the cells of an individual stem from the Zygote. These cells clearly differentiate into populations that assume particular functions, shapes and rates of turn over. These populations of cells are said to be

compartmentalized such that successive generation of cells in a given compartment may either remain constant or differentiate i. e. change their characteristics and establish a new population of cells. The process that initiates differentiation is termed induction. An inducer is the agent that persuades cells to be induced. Furthermore, each compartment of cells must be competent to respond to the induction process.

There is evidence that over time, populations of embryonic cells vary their competence from no response to maximum response and then back to no response. In other word, there

is a window of competence of varying duration for different population of cells. FORMATION OF THE 3LAYERED EMBRYO (i.e. the differentiation of the Primary Germ Layers) After fertilization, the mammalian development involves a phase of rapid proliferation and migration of cells with little or no differentiation. The proliferative phase lasts until 3 germ layers are formed. 1st Phase of Development After fertilization, the fertilized ovum travels through the oviduct and reaches the uterus. During this passage, the cells undergo rapid mitosis so that it forms a solid mass of 16 cells, which at this stage is called Morula.

With the ovum in the uterine cavity, fluid enters the morula and accumulates in an eccentric location. The fluid-containing cavity is now called Blastocoele and the embryo at this stage is called Blastocyst. Within the blastocyst, 2-cell population can now be distinguished. (1) Those lining the cavity (Primary Yolk-sac) are called Trophoblast cells and a small cluster of cells within the cavity called inner cell mass or Embryo blast. The embryo blast cells form the embryo proper whereas the trophoblast cells are associated with the implantation of the embryo and the formation of the placenta. As soon as the Blastocyst is implanted into the Uterine Endometrium, the embryo blast

rapidly differentiate into 2 layers so that at about 8 days, an outer ectodermal and an inner endodermal layer can be distinguished in the bilaminar germ disk resulting in formation of 2 cavities on either sides of the disk. In the next few days, further changes occur mainly in the bilaminar disk. The Amniotic cavity is formed by migration of the ectodermal cells while the secondary Yolk-sac is formed from the migration of the endodermal cells. This configuration is completed in 2 weeks of embryonic development. During the 3rd week the bilaminar disk is converted into a trilaminar disk through the development of the primitive streak in between the ectoderm and endoderm cells.

FORMATION OF THE NEURAL CREST AND THE FATE OF THE GERM LAYERS It has been established that the formation of the 3-layered embryo occurs during the 3-4 weeks of development. These initial events involve cell proliferation and migration. In the next 3-4 weeks of development, major tissues and organs differentiate from the 3layered (Triploblastic) embryo. The head, face and tissues contributing to the development of the teeth also differentiate during this period.

The major key events that occur during this period involve: (a) the differentiation of the nervous system and neural crest tissue from the Ectoderm, (b) the differentiation of mesoderm and (c) the folding of the embryo in 2-planes along the caudacephalic (tail-head) axis and lateral axis. The nervous system develops as a thickening within the ectodermal layer at the head - end of the embryo. This thickening constitutes the neural plate, which rapidly form raised margins, i.e. the neural folds. These folds in turn encompass and delineate an increased midline depression i.e. the neural groove. The folds eventually fuse so that a neural tube now separates from the ectoderm forming the floor of the

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amniotic cavity with mesoderm intervening. From the neural tube, the brain and the spinal cord develop. In the mammalian embryo, a group of cells separates from the lateral aspect of the neural plate and not from the crest but the name/term, neural crest cells, has been entrenched and retained for these groups of cells. These groups of cells (neural crest cells) have the capacity to differentiate extensively within the developing embryo giving rise to a number of structure, e.g. the sensory ganglia, sympathetic neurons, Schwann cells, pigment cells, meninges and the cartilage of the branchial arches. They also form most of the embryonic connective tissue in the facial region. The

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contribution of the neural crest cells is so extensive and their contribution so significant that they have been considered as a fourth (4th) germ layer. In a dental context, the proper migration of neural crest cells is essential for the development of the face and the teeth. In Treacher Collins Syndrome (mandibulofacial dysostosis) full facial development is prevented by interference in the migration of neural crest cells to the facial region. All the tissues of the teeth, except enamel, and its supporting apparatus are derived directly from neural crest; their depletion will prevent proper dental development.

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FOLDING OF THE EMBRYO This is a crucial developmental event. Folding occurs in 2 planes along the cauda-cephalic axis and the lateral axis. Head fold is crucial to the formation of the primitive stomatodeum (oral cavity). With this fold, ectoderm lines the oral cavity, which is separated from the gut by the buccopharyngeal membrane. The thin plate of mesoderm in the trilaminar embryo thickens on each side of midline to form paraxial mesoderm. At the periphery of the paraxial mesoderm, the mesoderm remains thin and this is the intermediate mesoderm. After this, another thickening of mesoderm occurs and this is the lateral plate mesoderm.

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Derivatives from the Mesoderm Paraxial Mesoderm: This forms segmental blocks somites and each somite contributes to 2 adjacent vertebrae and their disks, a segmental mass of muscles and the dermis of the associated skin. Intermediate Mesoderm: It gives rise to the urogenital system. Lateral Plate Mesoderm: forms the connective tissue of the muscles and viscera, the serous membrane of the pleura, pericardium and peritoneum, blood and lymph cells; and the cardiovascular and lymphatic system as well as spleen and adrenal cortex. As a result of lateral folding, the ectoderm of the floor of the amniotic cavity now encapsulates the embryo and forms the surface epithelium.

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The paraxial mesoderm remains adjacent to the neural tube and notochord. The lateral plate mesoderm cavitates to form a space (coelom) and the mesoderm bounding this cavity now lines the body wall and gut. The intermediate mesoderm becomes relocated to a position on the dorsal wall of the coelom. The Endoderm forms the gut. One of the derivatives of mesoderm is mesenchyme i.e. the embryonic connective tissue. The neural crest cells also give rise to mesenchyme, which is termed ectomesenchyme to distinguish it from other mesodermal mesenchyme. In summary, early stages of embryonic development involve

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rapid cell proliferation and some histodifferentiation leading quickly to the formation of a trilaminar disk consisting of 3 layers which are the ectoderm, mesoderm and endoderm with a head to tail axis fold established. The nervous system develops from the ectoderm of this disk through the development of folds. These folds also spin off neural crest cells that contribute extensively to many tissues of the embryo including most of the dental tissues. All the tissues of the embryo arise from these 4-cell populations. The shape of the embryo is determined by the folding of the disk in 2 planes along the caudacephalic and lateral axes with the head fold being crucial to the establishment of the primitive mouth.

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Environmental factors have relatively little impact on the production of congenital defects during the early stages of development because their effects are masked. If damage is slight, proliferative activity is so great that the damage can easily be compensated for by the replacement of new cells. If the damage is severe, the embryo dies. Environmental effects are however significant in the later stages of embryonic development.