NEURAL CREST CELLS

Cranial Neural Crest cells migrate into the head, face, and pharyngeal arch mesoderm in three distinct streams. 

Each stream differentiates into Cranial Nerve Ganglia and mesenchyme which forms much of the skeletal and connective tissue elements characteristic of each arch.

These streams also provide axonal guidance for nerves in the head & neck region.

Neural Crest cells are essential for the formation of much of the craniofacial region. There are many congenital defects associated with neural crest migration or

proliferation  failures.

Neural Crest cells, compared with mesoderm, are far more susceptible to teratogens, e.g., Alcohol, smoking, antiseizure medications,  folic acid deficiency, infections, and too much or too little retinoic acid.

Signaling Pathways

- Developmental Factors -

Rhombomeres express a specific pattern of Homeobox and other genes regulated by Retinoic Acid. 

Neural Crest cells carry these expression patterns into the face region and the pharyngeal arches.

The growth and patterning proteins, Sonic Hedgehog and FGF8,  play a major role in stimulating the proliferation of Neural Crest in this area.

CARTILAGE of Pharyngeal Arches 

1-Meckels

2- Reicherts 

3- Hyoid Bone

4 & 6- Larynx 

Occipital Somites

Occipital Somites also give rise to Trapezius & Sternocleidomastoid muscles

Pharyngeal Arch 1

- TRIGEMINAL NERVE

   Muscles of Mastication

    &  * “MATT” Muscles

* M = Mylohyoid

    A  = Anterior Belly of Digastric

    T  = Tensor Tympani

    T  = Tensor Veli Palatini

Pharyngeal Arch 2

Facial Nerce

               Muscles of Facial

                    Expression

                          &

              - Post Belly of Digastric

                 -  Stylohyoid

                 -  Stapedius

Pharyngeal Arch 3

Glossopharyngeal Nerve

MUSCLE:

Stylopharyngeus

Pharyngeal

Arches 4 & 6

             Muscles of Pharynx,

                Larynx, & Soft

                Palate;: 

 Except:

Stylopharyngeus (IX) & Tensor Veli Palatini (V) Muscles

Development of the Internal Ear

-Induction of surface ectoderm by the notochord

and then the paraxial mesoderm results in the

formation of the Otic Placode which forms the

Internal Ear 

Development of Middle Ear

-The Auditory Tube + Middle Ear & External Auditory Canal develop from Pharyngeal Pouch 1 and Pharyngeal Cleft 1, respectively

Auricle Develops from....

Pharyngeal Arches 1&2 

Rubella Infection during weeks 7 & 8

Rubella infection during weeks 7 and 8  may cause

defects in the Inner Ear (Organ of Corti) which result

in permanent congenital deafness.

Defective formation of Pharyngeal Arches 1 & 2

and/or Pouch 1 & Cleft 1 may result in Middle or

External Ear defects and deafness. Many of these

defects are repairable. 

Congenital Defects of Auricle

Auricular defects and Accessory

auricular nodulesare common.

Auricular defects may be

associated with deafness

(repairable)due to atresia of

External Auditory Meatus.

There is a significant correlation

between Auricular defects and

Kidney abnormalities.

PHARNGEAL ARCH DEFECTS

-Several syndromes involve hypoplasia of the mandible and maxilla etc. (1st arch syndrome or craniofacial dysostosis) as well as other pharyngeal arch structures.

Most involve insufficient amounts of Neural Crest Cells and are multifactorial in origin. Others, like Treacher-Collins Syndrome, are due to genetic mutations. 

TREACHER COLLINS SYNDROME

-Autosomal dominant condition which, amongst other defects, includes mandible & facial bone hypoplasia, malformation of external ears, cleft palate, & faulty dentition. 

Agnathia 

-An extreme form of Neural Crest hypoplasia is seen in Agnathia in which the lower jaw fails to form and the external ears fail to migrate out of the neck region.

PHARYNGEAL

 POUCHES

Pouch 1 develops into the Auditory

 Tube  and the Middle Ear Cavity

Pouch  2  develops into the Tonsillar Epithelium for the Palatine Tonsil. The tonsil itself is derived from mesoderm

Pouch 3 develops into the Thymus and

Inferior Parathyroid Glands

Pouch 4 develops into the Superior

Parathyroid Glands & Ultimobranchial Body.

The latter structure seeds the Thyroid gland

with calcitonin secreting “C”cells.

mesoderm

DiGeorge Syndrome,

DiGeorge Syndrome, a Neural Crest deficiency in which the Thymus and Parathyroids fail to partially or completely differentiate from Pouches 3 & 4,results in immune deficiencies with suppresse immunocompetence and hypocalcemia  in addition to  wide eyes, low ears, and  small jaw (1st arch syndrome). 

This syndrome is usually caused by a Chromosome # 22

deletion, but can also be produced by Diabetes or Alcohol.  Prognosis is

poor.

Rathke’s Pouch

Rathke’s Pouch is a DORSAL

Ectodermal outpocket from

the oral cavity which merges

with the neuroectoderm of the

Hypothalamus to form the

Anterior Lobe of the Pituitary

Gland.

Foramen Cecum

-The Foramen Cecum marks the boundary between  BODY and ROOT of the tongue.

Tongue Musculature arises from...

Tongue Musculature arises from Occipital

 Somites and is innervated by the

 Hypoglossal Nerve. Muscle migrates to the

 tongue along with its innervation.   

Thyroid Gland Originates from......

The THYROID GLAND originates from ENDODERM

 and descends from the  FORAMEN CECUM via the

Thyroglossal Duct to the anterior NECK region.  

Normally, the Thyroglossal Duct

regresses, leaving only a small Pyramidal

lobe extension where it was attached to

the gland. Remnants of the duct may

result in a Midline Thyrocervical Duct Sinus,

Cyst, &/or Accessory Thyroid Gland.        

CERVICAL

(Branchial)

SINUS

 The 2nd pharyngeal arch overgrows or

 covers the 3rd and 4th arches, often 

 leaving remnants of the space between.

 This  space (Cervical Sinus) may result 

 in the formation of Cervical Sinus Cysts

 &/or Fistulas in the neck.

Cervical Sinus Fistulas may open Internally

(most common) into the palatine tonsillar

area of the pharynx or  Externally into the skin.

Cervical (Branchial) Sinus Cysts

and/or Fistulas are located

anterior to the Sternocleidomastoid muscle.

Choroid Fissure and Optic Cup

Choroid Fissure forms along the Optic Stalk and Cup. Hyaloid Artery enters the

Fissure and ultimately becomes the Central Artery of the Retina.

Failure of the Choroid Fissure to

close will result in an unclosed Iris (Coloboma Iris)

and may result in other  defects.

Usually a genetic mutation.

Rubella infection during the 4th through

6th week

Rubella infection during the 4th through

6th week embryonic period may result in

congenital cataracts with opacity of the

developing lens and/or glaucoma.

Neuroectoderm (Optic Cup)

Neuroectoderm (Optic Cup)

 - Retina

  - Pigment layer

  - Iris

  - Ciliary Body

Mesenchyme for eye

Mesenchyme

 - Choroid Layer

  - Vitreous Body

  - Sclera

  - Cornea, Iris & Ciliary Body

    connective tissue

Surface Ectoderm for eye

Surface Ectoderm

   - Corneal Epithelium

    - Lens

Development of Olfaction

Cells from the placode  area migrate through the Pit to base of skull and develops into Olfactory Epithelium.

These migrating ectodermal and/or neural

crest cells also develop into Gonadotropin

releasing hormone (GnRH) cells which

migrate to the Hypothalamus. Cell death or

migration failure results in the Kallman

Syndrome characterized by Anosmia

& Hypogonadism. (X-chromosome; 1/10,000 males)

Palate

The Primary Palate is an

ingrowth (Medial Palatal

Process) from the Medial

Nasal Process.

The Secondary Palate

is derived from two (right &

left) Lateral Palatal Shelves.

The Incisive Foramen marks

the point of fusion between

Primary & Secondary

palates.

Nasal Septum

The Nasal Septum is a

Midline projection from the Frontonasal Prominence. It descends and connects with both the Primary & Secondary Palates at the midline raphe.

Cleft Lip And Cleft Palate

Cleft lip and cleft palate are considered separate

birth defects even though they often occur together.

Numerous combinations of facial clefts and degrees

of severity occur. The lip is formed at 8 weeks; the palate by 10 weeks.

Cleft formations are generally due to insufficient

numbers of Neural Crest (mesenchymal) cells.

The causes are multifactorial and include multiple

predisposing genes  &  teratogens including ROH,

smoking, antiseizure drugs (phenobarbital),  folic

acid deficiencies, infections, & excess retinoic acid

(vitamin A).