Peter A. Jezewski, DDS, PhDSTEVEN J. ZEHREN, PH.D.

Craniofacial Embryology; PHARYNGEAL APPARATUS, TONGUE &THYROID GLAND

NBDE Part I• Is a comprehensive exam• 400 questions

– Anatomic sciences (100):• Gross anatomy (49)• Histology (23)• Oral Histology (16)• Developmental Biology (11)• Professional Ethics/Patient Management (1)

– Biochemistry-physiology (100)– Dental Anatomy (100)– Microbiology-Pathology (100)

Axial Patterning Outline of CF Development

• to make it all more obvious• First ANTERIOR to POSTERIOR

– Early definition of head versus tail end. • Animal pole versus vegetal pole: ORAL always at animal pole.

– Gastrulation (in deuterostomes):• We are deuterostomes (Second mouth)

– Gastrulation (gut formation) = First mouth– Stomation (mouth formation) = second mouth

• From posterior (vegetal) pole of egg towards the animal pole or future anterior end.

• Defines germ layers– Ectoderm, mesoderm, endoderm

Axial patterning continued• Gastrulation: also DORSAL to VENTRAL

– Asymmetric gastrulation• Defines Dorsal to ventral axis, (and L and R too)

– Defines dorsal neural domain– Eventually defines dorsal anterior (cranial) region– Defines early neural crest specification; laterally to neural plate. Cranial

placodes are formed just ventrally to neural crest cells.

• Neurulation– Neural plate, CNCC, Cranial Placodes

• Pharyngeal stage– Pharyngeal arches 1, 2 and jaw formation: Primary, Secondary palate. – Tongue– Thyroid gland

A to P Axis

Deuterostomy• Primary AP axis, determined in the egg.• Mouth formation always at the Animal Pole,

coincident with the Anterior.

Ant

Post

Ani

Veg

Protostomes: Deuterostomes:

Diploblasts: Triploblasts:

Deuterostomy• Anterior mouth, Posterior Gut:• Protostomes = Common mouth and anus• Deuterostomes = Second mouth

– Gut at Posterior – Mouth at Anterior

Protostomes: Deuterostomes: Ant

Post

Diploblasts: Triploblasts:

Gastrulation => Posterior Gut formation =>

Germ layers• Ectoderm

– Skin, nervous system.

• Endoderm– Gut, liver, lungs.

• Mesoderm– Skeleton, muscles, heart, blood.

• A tissue centric hypothesis focusing upon cell types.

Human gastrulation

Anterior-Posterior Axial Differentiation: Hox genes

• Gene expression colinear between phyla.

D to V Axis too

Asymmetric Gastrulation => Dorsal and Ventral Tissues

• Dorsal Anterior Ectoderm– Neural tissue

• Dorsal Mesoderm– Notochord

• Ventral Mesoderm– Blood, muscle, bone

A lancelet - cephalochordate

Neurulation

• Neural plate is most dorsal neural tissue– Induced by dorsal mesoderm (notochord)

• Lateral to that is “less neural” tissue– Like regions that will form the neural crest, from

the lateral aspects of the neural plate

• Lateral to this are the regions that will induce the cranial placodes or preplacodal ectoderm

Epidermis Epidermis

Helms J A et al. Development 2005;132:851-861

Neurulation, CNCC formation

• existence of a common pre-placodal region• it seems that an initial step common to all placodes involve signals from the mesendoderm,

while later, more region-specific signals confer placode-specific properties.• induction of the pre-placodal domain

– Endoderm or mesoderm or neural plate

Cranial Placodes

Cranial Placodes

PHARYNGEAL ARCHES

Cranial Neural Crest Cells

Hox and Pharyngeal arches

R1 R2 R3 R4 R5 R6 R7 R8

CN V.

CN VII.

Cranial Neural Crest Cell Migration

AP and DV pharyngeal codes

End of Gastrulation => Phylotypic Stage

• Follows the blastula, gastrula, neurula stages.• At pharyngula stage, all vertebrates show remarkable

similarities:– notochord, – dorsal, hollow nerve cord, – post-anal tail,– series of paired branchial arches.

Comparative Embryology:Common Pharyngula Stage?

chicken

frog zebrafish

Non-mammalianMammalian

mouse

Mouth Formation

A

Site of midbrain

Lens placode

Nasal placode

Stomodeum Heart

Somites

Pharyngeal(branchial) arches

12

3 4

Slide 10.1

PHARYNGEAL ARCHES FORM DURING 4TH WEEK.ECTODERMAL GROOVES SEPARATE ARCHES ON OUTSIDE.

Max. prom.

Mand.prom.

Oropharyngeal membrane

Stomodeum(primitive oral cavity)

Ectoderm

Endoderm of pharynx

STOMODEUM & OROPHARYNGEAL MEMBRANE

Development of the craniofacial primordia.

Helms J A et al. Development 2005;132:851-861

Human primary, secondary palate formation

Mouse primary palate formation

Secondary palate formation

Frontonasalprominence

Umbilical vein

Spinal cord

Eye

Entrance to stomodeum

Entrance to intraembryonic coelom

Mandibular prominence

Second pharyngeal arch

Third pharyngeal arch

Fourth pharyngeal arch

Maxillary prominence

Slide 10.31 SCANNING EM OF EMBRYO (5TH WEEK)

B

Midbrain

1st pharyngeal pouch Aortic arches(1st to 4th)

Esophagus

Lung bud

Thyroid diverticulum(primordium of thyroid gland)

HeartTruncus arteriosus (commonarterial trunk from heart)

Esophagus

Dorsal aorta

Level ofsection C

Ectoderm Endoderm Mesoderm

Germ Layer Derivatives

Slide 10.2 ENDODERMAL PHARYNGEAL POUCHES SEPARATE ARCHES ON INSIDE

1st arch(Meckel)

2nd arch(Reichert)

Cartilages

Muscle

Nerve

Mandibular (1st) arch

1st pharyngeal(branchial) membrane

2nd pharyngeal pouch

3rd pharyngeal pouch

Mesodermal core of 4th arch

3rd aortic arch

Hyoid (2nd) arch

Germ Layer Derivatives

Ectoderm Endoderm Mesoderm

C

Slide 10.3 COMPONENTS OF A PHARYNGEAL ARCH

Human Pharyngeal Arch Cartilages

Pharyngeal arches

PHARYNGEL ARCH CARTILAGES: DERIVATIVES

NCC + and mesoderm boundary• NCC makes all anterior structures of face: including cartilage, bone, muscle.

• Mesoderm makes all those posterior to the pituitary gland

Pink = paraxialmesoderm derived.Blue = neural crest Cells derived.

MEMBRANE BONES OF ARCH 1

ZYGOMATIC

MAXILLA

MANDIBLE

SQUAMOUS TEMPORAL

Ear development

PHARYNGEAL ARCH MUSCLES: DERIVATIVES

• The muscles derived from arch 1 (green) include the muscles of mastication (eg, temporalis and masseter) and the mylohyoid and anterior belly of the digastric. Also derived from arch 1 are the tensor palati m. (soft palate) and tensor tympani m. (middle ear)(not shown).• All of the muscles of mastication insert into the mandible (also from arch 1).• The mylohyoid and anterior belly of the digastric also attach to the mandible. • The muscles derived from arch 2 (salmon) include the muscles of facial expression, stylohyoid m. and posterior belly of the digastric. Also derived from arch 2 is the stapedius m. (middle ear)(not shown).• 5. The muscle derived from arch 3 (purple) is the stylopharyngeus m.• The muscles derived from arch 4 (light blue) include most of the muscles of the pharynx and soft palate, as well as the cricothyroid m.• The muscles derived from arch 6 (dark blue) include most of the muscles of the larynx and the striated musculature of the esophagus (not shown).

PHARYNGEAL ARCH NERVES

(Arch 1)

(Arch 1)

(Arch 2)

(Arch 3)

(Arches 4 &6)

(Superior laryngeal br. and pharyngealbr. to arch 4; recurrent laryngeal br. to arch 6)

3rd, 4th, and 6th aortic arches

Spinal cord

Dorsal aorta

Pulmonary artery

Yolk stalk

Yolk sac

Midbrain

C

Slide 14.56PHARYNGEAL ARCH ARTERIES (AORTIC ARCHES)

Aortic sac

3rd aortic arch

Left dorsal aorta

Aortic arches

Right subclavian artery

Left subclavian artery

Truncus arteriosus(partly dividedaortic and pulmonaryarteries)

External carotid artery

Left dorsal aorta

Internal carotid artery

Aortic sac

3

4

Ductus arteriosus

Left dorsal aorta

4th aortic arch 6th aortic arch

Truncus arteriosus Aortic sac

Aortic sac

Dorsal aortae

3

45 6

5

6

A

7th intersegmental artery

B

Pulmonary arteries

Slide 14.57TRANSFORMATION OF AORTIC ARCHES (VENTRAL VIEW)

6 WKS 7 WKS

Right

3rd aortic arch

Left subclavian artery

Arch of aorta

Ligamentum arteriosum

Internal carotid arteries

Ascendingaorta

Pulmonary trunk

Brachiocephalic artery

Subclavian arteries

Right pulmonary artery

Ductus arteriosus

Descending aorta

Ascending aorta

External carotid arteries

Left common carotid artery

Left pulmonary artery

4th aortic arch 6th aortic arch

Truncus arteriosus Aortic sac Dorsal aortae

C D

Slide 14.58

8 WKS 6 MO. INFANT

TRANSFORMATION OF AORTIC ARCHES (VENTRAL VIEW)

Right

PHARYNGEAL POUCHES, GROOVES & MEMBRANES

A B

Opercular flap

(becomes incorporated into the thyroid gland and forms the parafollicular cells: secretes Calcitonin)

PHARYNGEAL POUCHES, GROOVES & MEMBRANES

Tongue

Foramen cecum of tongue

Tonsillar sinus and surface epitheliumof palatine tonsil(pouch II)

Larynx

Thymus (pouch III)

Auditory tube(pharyngotympanic tube)and tympanic cavity (pouch I)

Tract ofthyroglossal duct

Ultimobranchialbody (pouch IV)

Thyroid gland

Pouch III

Pouch IVParathyroidglands

Slide 10.1320 WEEK FETUS SHOWING DERIVATIVES OF PHARYNGEAL POUCHES

Undescendedparathyroid gland

Hyoid bone

Accessorythymic tissue

Thyroidcartilage

Superiorparathyroidglands

Persistent cordof thymic tissue

Ectopic inferiorparathyroid gland

Persistentthyroglossal duct

Thyroid gland

Trachea

Manubriumof sternum

Retrosternalthymus

Body of sternumSlide 10.19 CONGENITAL ANOMALIES OF THYROID, THYMUS & PARATHYROID GLANDS

LATERAL CERVICAL CYSTS(REMNANTS OF CERVICAL SINUS)

A BC

Epicardial ridge(SCM develops in it)

Sternocleidomastoidmuscle

Swelling formed bybranchial cyst

Tendon ofsternocleidomastoidmuscle

Slide 10.16

LATERAL CERVICALCYST. NOTE ITS

POSITION ANTERIORTO SCM MUSCLE.

TONGUE

A

Arches: Distal tongue bud

Median tongue bud

Foramen cecumof tongue

Copula

Hypobranchialeminence

Hypobranchialeminence

Rima glottidis(opening to vocalapparatus)

Median sulcus

Circumvallatepapillae

Terminal sulcus

Foramen cecum of tongue

Epiglottis

Pharyngeal part of tongue

Oral partof tongue

Migration of thirdarch mesoderm1

2

34

Esophagus Laryngotracheal groove

B

C

Arch Derivatives of Tongue

1st pharyngeal arch(CN V-mandibular division)

2nd pharyngeal arch(CN VII-chorda tympani)

3rd pharyngeal arch(CN IX-glossopharyngeal)

4th pharyngeal arch(CN X-vagus)

Slide 10.26 DEVELOPMENT OF TONGUE

4 WKS5 WKS

ADULT

Occipital myotomes

Orbicularis oculi Temporalis

Occipitalis

Auricularis

Stylohyoid

Stylopharyngeus

Anterior and posterior bellies of digastric muscle

Platysma

Orbicularis oris

Masseter

Mylohyoid

Pharyngealmuscles

SternocleidomastoidClavicle

Frontalis

Buccinator

A B

First archmuscles

Second archmuscles

Third archmuscles

Fourth and sixtharch muscles

Slide 10.9

ALL TONGUE MUSCLES (EXCEPT PALATOGLOSSUS)DEVELOP FROM OCCIPITAL MYOTOMES

(PA4)

1. Muscles of tongue (except palatoglossus) develop from occipital myotomes (palatoglossus derived from arch 4) (A).2. Myoblasts from these myotomes migrate into the tongue (arrow in Fig. A).3. XII accompanies the myoblasts during their migration and innervates the tongue mm.

THYROID GLAND

Slide 10.20

DEVELOPMENT OF THYROID GLAND (EARLY)

Esophagus

A

B

Pharyngeal pouches

Pharyngealarches

Laryngotrachealdiverticulum

Primordialpharynx

Thyroiddiverticulum

Esophagus

Oropharyngealmembrane

Tongue

Foramen cecum of tongue

Thyroglossal duct

Thyroid diverticulum

Developinghyoid bone

StomodeumFormer site oforopharyngealmembrane

Heart

4 WKS

5 WKS

1. Thyroid gland is 1st endocrine gland to appear (4 weeks) (A).2.Thyroid gland develops as a median, endodermal thickening in the floor of the pharynx; this thickening soon forms a down growth known as the thyroid diverticulum (A).3. Thyroid diverticulum descends in neck, anterior to developing hyoid bone (B).•Thyroid diverticulum remains connected to floor of pharynx (in region of tongue) by thyroglossal duct. The opening of the duct onto the tongue is the foramen cecum (B).

Slide 10.21

DEVELOPMENT OF THYROID GLAND (LATER)

C

D

Tongue

Foramen cecum

Thyroglossal duct

Site of atrophyof duct

Thyroid gland

Soft palateHard palateForamen cecumof tongue

Former tract ofthyroglossal duct

Hyoid bone

Larynx

Thyroid glandPyramidal lobeof thyroid gland

Hyoid bone

Trachea

6 WKS

ADULT

1. By 7 weeks (slightly later than stage shown in Fig. C), thyroid gland has assumed its adult shape and position and the thyroglossal duct has atrophied.2. In adult (D), thyroid gland has two lateral lobes connected by an isthmus. Dashed line represents former tract of thyroglossal duct. Distal part of duct may persist (~50%) as a pyramidal lobe.

A

Thyroglossal duct cyst

Opening of thyroglossal duct sinus Cervical thyroglossal duct cyst

BThyroid gland

Foramen cecum of tongue

Hyoid bone

Hyoid bone

Lingualthyroglossalduct cyst

Thyroid cartilage

Slide 10.22

THYROGLOSSAL DUCT CYSTS AND FISTULA (SINUS)NOTE MIDLINE POSITION OF CYSTS

1. Thyroglossal duct normally degenerates but a portion of it may persist to form a thyroglossal duct cyst (A,B).2.These cysts may occur anywhere along the former tract of the thyroglossal duct (dashed lines in Figs. A & B). However, these cysts are always located close to, or in, the midline (vs. lateral cervical cysts).3.If a cyst communicates w/ the surface of the neck it is termed a thyroglossal duct fistula (sinus) (A). Usually such a fistula occurs secondarily (after rupture of an infected cyst).4. Most thyroglossal duct cysts are observed by 5 years of age.

END OF LECTURE