Human Facial Development

• This chapter examines human face and oral cavity development through amphibian, avian, and mammalian embryo studies.
• Early facial development is similar across vertebrates, involving cell migration, interactions, growth, and differentiation.
• Research helps understand developmental abnormalities causing common human malformations.

Origin of Facial Tissues

Formation of Germ Layers

• After fertilization, a morula forms.
• In mammals, most cells form extraembryonic structures (placenta), while the inner cell mass differentiates:
  • Epiblast forms the entire embryo.
  • Hypoblast contributes to placental support.
• The primitive streak produces three germ layers:
  • Endoderm contains notochordal and prechordal plates.
  • Mesoderm migrates from the epiblast.
  • Ectoderm remains in the epiblast.

Neural Induction and Mesodermal Differentiation

• Chorda mesoderm induces the neural plate from ectoderm for brain and spinal cord development.
• The prechordal plate might play a similar role in the anterior neural plate region.
• Neural plate induction is influenced by diffusible substances and cell interactions.

Neural Crest Cell Migration

• Neural crest cells form at the neural plate's edges and migrate extensively.
  • Trunk neural crest cells develop into neural, endocrine, and pigment cells.
  • Cephalic neural crest cells form skeletal and connective tissues (cartilage, bone, dentin, dermis).
• Tooth enamel is the facial connective tissue not from neural crest cells, forming from ectoderm.
• Crest cells migrate in sheets under the ectoderm, surrounding mesodermal cores in visceral arches.

Vascular Development

• Capillary endothelial cells from mesoderm invade crest mesenchyme to form blood vessels.
• Pericytes closely associate with endothelial cells as initial support.
• Crest cells differentiate into fibroblasts and smooth muscle cells to form vessel walls later.
• Vascular networks modify before becoming the mature vascular system.

Muscle Development

• Most myoblasts originate from the mesoderm and form striated muscle fibers.
• Hypoglossal muscles derive from somites near the developing hindbrain.
• Extrinsic ocular muscles come from the prechordal plate and migrate to somitomeres near the ear.
• Facial muscle connective tissues come from neural crest cells.

Epithelial and Glandular Development

• Epithelial structures (glands, enamel organ of teeth) form through ectodermal invagination into mesenchyme.
• Connective tissue components of these structures (fibroblasts, odontoblasts) come from neural crest cells.

Development of Facial Prominences

• After crest cell migration and vascularization, facial prominences appear.
• Upper facial prominences contribute to the primary and secondary palates.

Development of the Frontonasal Region

• Olfactory placodes appear in the frontonasal region from the anterior neural plate.
• Lateral nasal prominence (LNP) moves forward to meet the medial nasal prominence (MNP).
• Maxillary prominence (MxP) grows from the first visceral arch and merges with LNP and MNP.
• Their fusion forms the primary palate, separating oral and nasal cavities.
• The primary palate contributes to the upper lip, anterior maxilla, and upper incisor teeth.
• The external nose develops from prominences.

Development of Maxillary Prominences and Secondary Palate

• Palatal shelves grow from the medial edges of MxPs, initially positioned beside the tongue.
• Shelves elevate, contact, and fuse above the tongue around week 9.
• Anterior shelves elevate via rotation, while posterior shelves change shape.
• Fusion of shelves involves:
  • Stopping cell division at the medial edges.
  • Loss of peridermal cells.
  • Adhesion via extracellular glycoproteins.
• Epithelial seam cells undergo cell death or mesenchymal transformation.
• Most hard and soft palates develop from the secondary palate.

Development of Visceral Arches and Tongue

Visceral Arches Formation

• Humans have six visceral arches (the 5th is rudimentary).
• The proximal first (mandibular) arch forms the MxP.
• As the heart moves caudally, the mandibular and hyoid arches merge in the midline.

Neural and Muscular Development

• Cranial nerves (5th, 7th, 9th, 10th) extend into visceral arches.
• Myoblasts originate from the mesoderm near the neural tube and migrate into arches.
• Facial muscles include:
  • 2nd arch myoblasts form facial expression muscles (7th cranial nerve).
  • 1st arch myoblasts form mastication muscles (5th cranial nerve).
  • 3rd & 4th arch myoblasts form pharyngeal & soft palate muscles.
• Skeletal and connective tissues arise from neural crest cells.

Tongue Development

• Forms in the ventral pharyngeal floor.
• Covered by:
  • Ectoderm (anterior two-thirds).
  • Endoderm (posterior one-third).
• Hypoglossal muscle cells arrive before lingual swellings appear.
• The thyroid gland arises from the thyroglossal duct at the foramen cecum.

Glandular and Ear Development

• Endoderm-derived glands include the thyroid, parathyroid, and thymus.
• Ectoderm-derived glands include the salivary and anterior pituitary glands.
• The Eustachian tube forms from the groove between the 1st and 2nd arches.
• The external ear (pinna) develops from 1st and 2nd arch tissues.

Final Differentiation of Facial Tissues

• Cell migrations lead to inductive interactions, resulting in further differentiation.
• Neural crest cells:
  • Form cartilages, bones, and connective tissues.
  • Play a dominant role in facial development.

Tooth formation:

• Mesenchymal crest cells contribute to the dental papilla and tooth-supporting tissues.
• The epithelial-mesenchymal interaction determines tooth type (incisor, molar).
• Bone formation begins by week 8, marking the end of the embryonic period.
• The section addresses clinical issues related to embryonic facial development defects, especially facial clefts, hemifacial microsomia, Treacher Collins syndrome, lingual anomalies, and developmental cysts.

Facial Clefts

• Cleft lip and palate: The two major types are:
  • Cleft lip with or without cleft palate which can be related to deficient medial nasal prominences (MNPs).
  • Isolated cleft palate which is more related to the underdevelopment of the maxillary prominence (MxP).
• Environmental factors like maternal smoking and phenytoin use during pregnancy are linked to increased clefting rates.
• Animal studies show that hypoxia or drug exposure can disrupt morphogenetic movements, leading to abnormal nasal and palatal development.
• Cleft palate formation can result from a failure of palatal shelves to elevate, inadequate shelf growth, or failure of epithelial seam fusion.
• Rarer facial clefts occur because of fusion failures of facial prominences and may be associated with amniotic membrane abnormalities.
• Evidence suggests epithelial-mesenchymal interactions contribute to facial abnormalities.

Hemifacial Microsomia

• Characterized by underdevelopment of the temporomandibular joint, external/middle ear, and associated structures.
• Often associated with vertebral anomalies and cleft lip/palate, classified as oculoauriculovertebral syndrome.
• Possible causes include retinoic acid (Accutane) exposure in utero, affecting neural crest cell development.
• Similar defects were observed in fetuses of women who used thalidomide.

Treacher Collins Syndrome

• An inherited disorder due to a dominant gene.
• Causes underdevelopment of maxillary, mandibular, and hyoid prominence-derived structures.
• Ear anomalies and secondary cleft palate occur in one-third of cases.
• Likely results from ganglionic placodal cell defects, which secondarily affect neural crest cells.

Lingual Anomalies

• Median rhomboid glossitis: A red, smooth midline area on the tongue due to persistent tuberculum impar.
• Bifid tongue: Results from the failure of lateral lingual prominences to fuse.
• Lingual thyroid nodule: Caused by the failure of thyroid tissue to descend, leaving thyroid remnants at the tongue base.

Developmental Cysts

• Cysts arise from epithelial remnants after fusion of facial/oral prominences or embryonic structures.
• Branchial cleft cysts/fistulas: Occur laterally in the neck from visceral arch epithelium remnants.
• Thyroglossal duct cysts: Form anywhere along the thyroid descent pathway, typically near the midline.
• Globulomaxillary cysts: Arise from fusion areas of medial, maxillary, and lateral nasal prominences.
• Nasolabial cysts: Originate near the base of the nose, possibly from nasal glands or nasolacrimal duct epithelium.

Clinical Relevance to Cardiac Development

• Neural crest cell defects affecting craniofacial structures may also impact heart development.
• The spiral septum, which partitions the outflow tract of the heart, derives from neural crest cells, linking facial and cardiac anomalies.

Summary of Early Fetal Development and Craniofacial Formation

Early Development of the Fetus

• Fertilization initiates cleavage (cell division), leading to morula formation.
• The trophoblast (outer cell mass) nourishes the embryo, and the embryoblast (inner cell mass) develops into the fetus.
• The bilaminar embryonic disk (epiblast and hypoblast) transforms into a trilaminar disk via gastrulation, driven by the primitive streak.
• Notochord formation induces neural plate development, initiating neurulation.
• Mesoderm differentiates into paraxial, intermediate, and lateral plate mesoderm, giving rise to somites (dermis, muscles, bones).

Neural Crest Cells

• Multipotent cells contribute to odontoblasts, melanocytes, ganglia, adrenal medulla, thyroid parafollicular cells, connective tissue, blood vessels, and the conotruncal septum of the heart.
• Neural crest migration is crucial for normal head development.

Development of Pharyngeal Arches

• Embryonic folding positions the developing head cranial to the cardiac bulge, with the stomodeum (primitive mouth) in between.
• Pharyngeal arches contribute to the face and neck, each containing a skeletal element, artery, muscle, and nerve.
• Ectodermal clefts and endodermal pouches between arches develop into key structures.

Development of the Face

• Facial prominences (frontonasal, maxillary, and mandibular) shape the face.
• Olfactory placodes arise in the frontonasal process, forming nasal sacs and contributing to nasal structures.
• Fusion of stomodeum-bounding prominences completes facial formation.

Derivatives of Pharyngeal Arches

• First arch (Mandibular arch): muscles of mastication, Meckel's cartilage, and part of the mandible, supplied by the mandibular nerve.
• Second arch (Hyoid arch): muscles of facial expression, Reichert's cartilage, supplied by the facial nerve.
• Third arch: stylopharyngeus muscle, supplied by the glossopharyngeal nerve.
• Fourth & Sixth arches: laryngeal cartilages, supplied by superior and recurrent laryngeal nerves.
• Pharyngeal clefts and pouches form external acoustic meatus, middle ear, tonsils, parathyroid glands, and thymus.

Development of the Tongue

• Formed by tuberculum impar, lingual swellings (first arch), and hypobranchial eminence (third and fourth arches).
• The sulcus terminalis marks fusion.
• Muscles originate from occipital myotomes, supplied by the hypoglossal nerve.

Development of the Palate

• The primary palate forms from the frontonasal process.
• The secondary palate forms from maxillary palatal shelves, which fuse to complete the palate.

Clinical Considerations

• Cleft Lip & Palate:
  • Genetic and environmental factors (e.g., smoking, phenytoin).
  • Defects in the nasal or maxillary process development lead to clefting, which can be unilateral, bilateral, or associated with cleft palate.
  • Rare clefts result from fusion failures.
• Neural Crest Defects:
  • Retinoic acid exposure affects neural crest cells, leading to external and middle ear malformations (e.g., hemifacial microsomia).
  • Treacher Collins syndrome involves mandibular and facial abnormalities due to neural crest disruption.

Lingual Anomalies

• Median rhomboid glossitis persists tuberculum impar.
• Bifid tongue results from the failure of lateral lingual prominences to fuse.
• Lingual thyroid results from the thyroid tissue persisting at the tongue base.
• Developmental Cysts:
  • Branchial cleft cysts (neck), nasolabial cysts (near nose), and fusion line remnants may develop into cystic structures.

Notes on the Development of the Face

Timeline of Development

• 4th week: The human face begins to form.
• 6th week: The external face is completed.
• 6th - 8th week: The palates develop.
• 12th week: The soft palate is completed.

Facial Processes

• The face develops from five swellings (processes) around the primitive mouth (stomatodium).
  • Frontonasal process (single)
  • Maxillary processes (paired)
  • Mandibular processes (paired)
  • Made up of mesenchymal cells derived from neural crest cells.
  • Neural crest cells from the midbrain and forebrain develop the Frontonasal process
  • Neural crest cells from the midbrain and hindbrain develop the Maxillary and mandibular processes
• Frontonasal process develops the forehead, bridge of the nose, nasal cavity, nasal septum, and philtrum.
• Maxillary processes develops the lateral upper lip and upper cheek.
• Mandibular processes develops the lower lip, lower jaw, and lower cheek.

Early Embryonic Structures

• By the 4th week, prominences on the ventral aspect of the embryo:
  • The head prominence develops the brain.
  • The pericardial prominence develops the heart.
• The groove between these two prominences is called the stomatodium.
• Deep these is the developing foregut.
• Pharyngeal arches (curved cylindrical mesodermal structures) develop on each side of the foregut:
  • The first pharyngeal arch (Mandibular arch) is important for face formation.
  • The second pharyngeal arch (Hyoid arch) contributes to facial structures.
• Oropharyngeal (Buccopharyngeal) membrane:
  • Separates the stomatodium from the foregut.
  • Breaks down in the 4th week, establishing communication between the oral cavity and foregut.

Formation of Facial Processes

Frontonasal Process Formation

• Mesenchyme from the forebrain and midbrain proliferates forward and downward.
• This projection overlaps the upper stomatodium and becomes the frontonasal process.

Maxillary and Mandibular Process Formation

• The Mandibular arch (1st arch) gives off a bud from its distal end which creates the Maxillary process.
• The remaining part of the arch is called the Mandibular process.
  • The Maxillary process is the Dorsal projection.
  • The Mandibular process is the ventral projection.
• Five primordia for facial development:
  • Frontonasal process
  • Maxillary processes (paired)
  • Mandibular processes (paired)

Development of the Nasal Structures

• The end of 4th week shows bilateral nasal placodes appearing as localized thickenings on the frontonasal process.
• Nasal placodes invaginate and form nasal pits.
• Edges elevate which forms:
  • Medial nasal processes.
  • Lateral nasal processes.
• The lateral part of the raised edges forms the lateral nasal process.
• All placodes, medial nasal, and lateral nasal are all derivatives of the frontonasal process.
• Medial nasal process has an enlarged lower end called the globular process.

Formation of the Lips

• Lower Lip Formation
  • Both mandibular processes from both sides grow towards the midline, forming the margin of the stomatodium.
• Upper Lip Formation
  • Each maxillary process grows medially.
    • Fuses with lateral nasal process.
    • Fuses with medial nasal process.
• Then medial and lateral processes fuse.
• Nasal pits become external nares
• Maxillary enlarges while frontonasal narrows, brings nares together.

Composition of the Upper Lip

• The mesodermal and ectodermal components of the lateral part of the upper lip come from the maxillary process.
• The mesodermal component of the median part comes from the frontonasal process.
• The ectodermal part comes from the maxillary process.
  • The skin of the upper lip is innervated by the maxillary nerve.

Contribution of the Second Pharyngeal Arch

• The muscles of the face come from the mesoderm of the second pharyngeal arch.
• Facial nerve supplies it.

Formation of the Cheeks

After lip form, stomatodium remains broad laterally.

Maxillary and mandibular fuse. Maxillary forms the greater and upper part. Mandibular forms the smaller lower part.

Formation of the Nasolacrimal Duct

• Maxillary fuses with the lateral and medial and the medial angle.
• Forms a groove Forms the nacolacrimal duct.

Development of the Eyes

• Eye first lens pladode
• The lens placode appears ventrolateral to forebrain.
• It detachaes from ectoderm.
• Forms the bulging of the developing eye.
• eyes are positioned laterally.
• Frontonasal narrows, eyes move medially.
• Eyelids form from ectodermal, mesoderm within.

Formation of the Nose

• Nose forms with contributions from frontonasal and medial and lateral nasal. Nostrils form when pits are cut off from fusion.
• frontonasal narrows, and the nares move together.
• cavity form from extension of nasal pits.

Development of the Nasal Cavities

• cavity form from extension of nasal pits. pIts arise from nasal placodes.
• the frontonasal process lies between pits.
• Processes fuse forming a horizontal partition between the and stoma.
• The primitive palate is derived from the frontonasal.

Formation of the Nasal Structures

Nasal pits deepen.

• Nasal sacs expand.

• bucconasal, stomato then breaks down

• ventral opening forms communicates from the exteior.

• posterior form the primitive nasa aperture.

• Nasal sacs are widely separated by the frontonasal process.

• That the process narrows, the nasal comes ether.

• Tissue thins down.

Derivatives of the Nose and Cavities

Lateral wall is processes. Olfactory is olfactory. Bridge from frontonasal. Nostrils from pits. Cavity sacs elongate.

Formation of the External Ear

Swelling called hillocks. Form at the first groove. The cleft is the external. Ear forms under jaw. man fails, affects the ear.

• Definitive palate
• Palates
• processes

V-shape. Lineshape.

• Septum

• Anterior ossifies.

• posterior is nonossified

• -- is uvula. Face Development

• Pro: max to medial.

• Bi is both.

• Midline is most def.

• Fail is is

• Hair lip.

• Medil is fusion failure.

• Bis is bi. Mid is dev. Fail for processes result. Fail max by medial. Duct not formed.

Processes fail. Cleft forms from mouth to ear. Mouth is wid.

• Small is micro.

Sep at front. Tube. Fails eyelid-max-mand-re. Recede and agnat.

Hypertelorism Wide

Lip Anomalies Pits

Palate Defective Two

• Passes through Not thru

Fails bi plat, y cleft Fails one plat, one side sep. Plat. Hard extnd Soft is limited Yuck if its only the yuck.