introduction to craniofacial development

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Introduction to Craniofacial Development

The Organisation of the Pharyngeal Apparatus

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Learning Objectives

By the end of these sessions, you should be able to:

1. Describe or illustrate the organisation of the pharyngeal apparatus.

2. Identify examples of structures that develop from each of the pharyngeal arches.

3. Describe how structures in the first pharyngeal pouch contribute to communication.

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"It is not birth, marriage, or death, but gastrulation, which is truly the most

important time in your life."            

Lewis Wolpert (1986)

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• During the pre –Embryonic period, the cells that will eventually give rise to all structures of the body differentiate into three germ layers.

• During this stage (Gastrulation), cell movements result in a massive reorganization of the embryo from a simple spherical ball of cells, the blastula, into a multi-layered organism.

• Many of the cells at or near the surface of the embryo move to a new, more interior location.

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• The cells of the embryo form three tissue (germinal) layers:

- Ectoderm (outside layer),

- Mesoderm (middle layer),

- Endoderm (inside layer).

• This is one of the most crucial points in development where a great deal of differentiation occurs.

Ectoderm

Mesoderm

Endoderm

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• These specialized layers of cells are:

- Ectoderm (forming all nerve and some epithelial tissue),

- Mesoderm (forming all connective, muscle and some epithelial tissue)

- Endoderm (forming some epithelial tissue)

• These cells undergo rapid regional development in the embryo, producing the precursors of adult structures

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Zygote

Blastula

EndodermEctoderm

Gastrula

Epidermis & associated structures

(skin, hair, nails etc)

Brain & NS Embryonic gut

Inner lining of digestive tract

Inner lining of respiratory

tract

Glands including liver & pancreas

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Mesoderm

Notochord Somites

Mesenchyme

(loose migratory cells)

Muscle Outer covering of internal organs

Excretory organs Gonads

Dermis (inner skin layer)

Bones & cartilage

Circulatory system (heart, blood vessels)

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• At the end of Week 3, ectoderm differentiates into neuroectoderm and epidermis. The latter covers the outside of the body.

• Signals from the underlying mesoderm cause the now neural precursor cells called the neural plate to invaginate and form a neural tube

• Neuroectoderm forms neural tube and neural crest. • Hollow neural tube eventually becomes the central

nervous system (top of tube becoming the brain and farther down, the spinal cord).

• When the neural tube forms, the intermediate cells between the tube and the ectoderm become neural crest cells.

• Neural crest cells are migratory and begin leaving the neural crest at about Week 5 to reach various target areas where further specialization occurs (see Fig. ).

• These cells migrate out and become cells of the peripheral nervous system

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• Just beneath the neural tube lies another structure, the notochord.

• This notochord functions as the midline segmental organiser for all of embryologic development.

• As adults, only vestigial remnants of this once dynamic notochord remain.

• However a line of function, a midline that organises our physiology, persists to guide us throughout life.

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• As the development of the head progresses, neural crest cells (and lateral plate mesoderm) both migrate into rapidly forming pharyngeal arches, a series of bump-like structures on both sides of the embryonic head (see Fig.)

• Neural crest cells, in addition to forming nerve tissue, produce the bones of the cranium.

• Within the pharyngeal arches, neural crest cells and lateral plate mesoderm give rise to bones of the jaw and lower face, the viscerocranium (see Fig.).

• Lateral plate mesoderm also contributes to the formation of the cartilages of the larynx

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Pharyngeal Apparatus

• The key to understanding craniofacial development are the Pharyngeal Apparatus (PA)

• Also known as Branchial Apparatus

• Pharyngeal Apparatus include:

- Pharyngeal arches (mesoderm)- Pharyngeal clefts (ectoderm)- Pharyngeal pouches (endoderm)- Pharyngeal membranes

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Pharyngeal Apparatus

• This structure contributes extensively to development of structures in the head and neck.

• 3 developmental layers come together to form the PA• In the 4th weeks of embryological development:

- swellings form at rostral end (head end)

- by end of 4th week all swellings (PA) have appeared

from mesoderm

- 3 germinal layers are apparent:

1. Ectodermal lining: skin

2. Endodermal lining: internal surface

3. Mesodermal core

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Organisation of the Pharyngeal Apparatus

Pharyngeal Arches:

- Out pocketings of surface ectoderm that are lined on the inside by endoderm.

- Contain mesoderm in between.

Ectoderm

Mesoderm

Endoderm

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• The PA consists of 4 pharyngeal arches, pharyngeal pouches and pharyngeal grooves.

• Neural crest cells in the cranial region migrate to the pharyngeal apparatus

• They cause enlargement of the arches and these cells contribute to the development of bones and connective tissues of the head and neck.

• Pharyngeal arches develop into components of the face.

• Arch mesoderm forms muscles of face

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Components of the Pharyngeal Arches I

• 6 arches develop. We study 4 as the 5th arch degenerates and the 4th and 6th arches fuse to form one

• Each pharyngeal arch has its own vascular supply, cranial nerve innervation, muscular components and skeletal components (cartilage).

• Grooves separate arches externally. Pouches separate arches internally.

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Pharyngeal Arch 1:

• First arch splits giving rise to 2 regions:- Rostral part called Maxillary Process- Caudal region called Mandibular Process

• Maxillary process gives rise to upper jaw (Maxilla)

• Mandibular process gives rise to lower jaw (Mandible)

• The first pharyngeal arch is often called the mandibular arch. It is from this arch that the jaws develop.

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Pharyngeal Arch 2:

• Often called the hyoid arch as part of the hyoid bone develops here.

Where is the hyoid bone located and how is it important to communication?

• Hyoid bone acts as a movable base for tongue. It is an attachment point for neck muscles that raise and lower larynx during swallowing and speech

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Components of the Pharyngeal Arches II

• The remaining parts of the hyoid bone develop in the third pharyngeal arch and the fourth pharyngeal arch and contributes to development of laryngeal cartilages.

• It can be seen that each pharyngeal arch contributes to the development of structures that will play a role in communication.

• In first arch syndromes (e.g. Treacher collins syndrome), there may be underdevelopment of first arch structures. Identify ways in which this may affect communication I

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Pharyngeal Arch

Cranial Nerve

Muscle derivative

Skeletal Derivative

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Mandibular

Trigeminal nerve Muscle of mastication

Tensor tympani

Incus, ant. Lig of malleus

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Hyoid

Facial nerve Muscles of facial expression

Stapes,

Hyoid bone

3 Glossopharyngeal nerve

stylopharyngeas Horns of hyoid

4 Vagus nerve Striated muscles of oesophagus

5 None none none

6 Merges with 4

31View of a 24-week foetus illustrating the adult derivatives of the arch cartilages.

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Sketch of the head and neck regions of a 20-week foetus, dissected to show the muscles derived from the pharyngeal arches.

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The Pharyngeal Pouches:

• A human embryo has five pairs of pharyngeal pouches although only 4 develop.

• Composed of Endoderm

• Only the first pharyngeal pouch develops into structures that will have an impact on communication.

• The first pharyngeal pouch develops into a tubotympanic recess that subsequently develops into the Middle ear cavity, the Tympanic membrane and the Eustachian tube

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Pharyngeal

Pouch

Derivative

1 Epithelium of tympanic cavity and auditory tube

2 Epithelium of tonsil

3 Inferior parathyroid glands and epithelium of thymus

4 Superior parathyroid glands.

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Schematic sagittal section of a head, neck and upper thoracic regions of a 20-week fetus, showing the adult derivatives of the pharyngeal pouches

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Pharyngeal Clefts (grooves):

- located between arches

- these are spaces, thus contain no germ layer components

- initially 4 clefts of which only one develops as 2nd arch grows over all other clefts filling them in

- 1st cleft forms the External Auditory Meatus

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Pharyngeal Membranes:

- sites on bottom of arches

- where ectoderm is joined to endoderm

- 4 membranes initially

- as most clefts are filled in, only first membrane develops.

- this lies close to external auditory meatus and develops into the Tympanic membrane

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Patterning of the Craniofacial Region• Differential growth among various rudiments determines

development of a normal or abnormal face.• 2 factors determine morphogenesis:

- Genetic- Environment

• Differential growth controlled by differences in cell behaviour:

- cell death- cell migration- change in shape- change in size etc

• If any of these are perturbed, likely outcome is some type of birth defect

• Of the approximately 5,000 known human inherited conditions, over 700 are craniofacial abnormalities.

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• Regulation of cell behaviour conducted by secreted chemical factors (growth factors etc)

• These molecules are diffusable within the embryo

• They bind to receptors on cells and initiate signalling pathways within cells

• This results in regulation of gene expression (stimulate or suppress transcription factors)

• One class of transcription factors involved in patterning of craniofacial region:

- Homeotic or Hox genes

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• A series of homeotic genes known as Hox genes are known to play an important role in craniofacial development.

• These sequences of genes act as regulators of other genes; when they are affected, the function of other genes are affected.

• These genes expressed in hindbrain region.• Neural crest cells migrate out and carry pattern with

them to Pharyngeal Arches• Hox genes encode transcription factors, including Msx-

1, Msx-2, Dlx1-6, and Barx-1. • Thus a defect in Hox genes results in a defect in neural

crest cells and this affects the craniofacial region.

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• Proper craniofacial development requires the orchestrated integration of multiple specialized tissue interactions.

• Recent analyses suggest that craniofacial development is not dependent upon neural crest pre-programming as previously thought but is regulated by a more complex integration of cell and tissue interactions.

• In the absence of neural crest cells it is still possible to obtain normal arch patterning indicating that neural crest is not responsible for patterning all of arch development.

• The mesoderm, endoderm and surface ectoderm tissues play a role in the patterning of the branchial arches, and there is now strong evidence that Hoxa2 acts as a selector gene for the pathways that govern second arch structures.

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Congenital Malformations Of The Pharyngeal Apparatus

• Relatively uncommon

• First Arch Syndrome: malformation of the eyes, ears due to an insufficient migration of neural crest cells into 1st pharyngeal arch

• Treacher Collins Syndrome: defects of lower eyelids, deformed external ears

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Cleft Lip/Palate• The lip usually closes by 5 to 6 weeks after conception,

and the palate by 10 weeks.• The lip or the lip and palate together fail to close in

approximately 1 in every 1,000 babies born.• Cleft lip/palate occurs more often among Asians (about

1.7 per 1,000 births) and among certain groups of American Indians (more than 3.6 per 1,000 births).

• Males are affected more frequently than females.

Cleft palate• occurs alone less often, appearing in approximately 1 in

2,000 babies.• Unlike the risk for cleft lip/palate, the risk for isolated cleft

palate appears to be similar across all racial groups.• Another difference from cleft lip/palate is that females are

affected more often than males.