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
• Describe or illustrate the organisation of the
  pharyngeal apparatus.
• Identify examples of structures that develop from
  each of the pharyngeal arches.
• 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
Gastrula
Endoderm
Ectoderm
Epidermis associated structures (skin, hair,
nails etc)
Brain NS
Embryonic gut
Inner lining of respiratory tract
Inner lining of digestive tract
Glands including liver pancreas
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Mesoderm
Notochord
Somites
Outer covering of internal organs
Muscle
Excretory organs
Gonads
Mesenchyme (loose migratory cells)
Bones cartilage
Circulatory system (heart, blood vessels)
Dermis (inner skin layer)
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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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View 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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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.