UNSW Embryology

Head and Neck Development

© Dr Mark Hill (2008)

Acknowledgements

Introduction

The head and neck structures are derived from pharyngeal arches 1 and 2.

Each arch contains similar components derived from endoderm, mesoderm, neural crest and ectoderm. These components though will form different structures dependent upon which arch they are within.

The cavity within the pharyngeal arches forms the pharynx.

The pharynx contributes to 2 endocrine organs, in the roof the pituitary (hypophysis) and the floor the thyroid. The thyroid gland being one of the first endocrine organs to be formed has an important role in embryonic development. The pharynx floor of all arches also contribute to the formation of the tongue.

Because the head contains many different structures also review notes on Special Senses (eye, ear, nose), Respiratation (pharynx), Integumentary (Teeth), Endocrine (thyroid, pituitary).

Some Recent Findings

Schlosser G. Evolutionary origins of vertebrate placodes: insights from developmental studies and from comparisons with other deuterostomes. J Exp Zoolog B Mol Dev Evol. 2005 Jul 15;304(4):347-99.

Melnick M, Witcher D, Bringas P Jr, Carlsson P, Jaskoll T. Meckel's cartilage differentiation is dependent on hedgehog signaling. Cells Tissues Organs. 2005;179(4):146-57.

Matsuoka T, Ahlberg PE, Kessaris N, Iannarelli P, Dennehy U, Richardson WD, McMahon AP, Koentges G. Neural crest origins of the neck and shoulder. Nature. 2005 Jul 21;436(7049):347-55.

Richman JM, Lee SH. About face: signals and genes controlling jaw patterning and identity in vertebrates. Bioessays. 2003 Jun;25(6):554-68. Review.

Wilkie AO, Morriss-Kay GM. Genetics of craniofacial development and malformation. Nat Rev Genet. 2001 Jun;2(6):458-68.

Reading

Human Embryology (3rd ed), WJ. Larsen Chapter 12 Development of the Head, the Neck, the Eyes, and the Ears pp349 - 418. The Developing Human: Clinically Oriented Embryology (7th ed) Moore & Persaud Chapter Chapter 10 The Pharyngeal Apparatus pp201 - 240. Before we Are Born (5th ed.) Moore and Persaud Ch Essentials of Human Embryology Larson Ch Human Embryology Fitzgerald and Fitzgerald Ch UNSW Embryology Face Development | Selected Head and Neck References Additional References- Selected

Objectives

• List the main structures derived from the pharyngeal arches, pouches and clefts.
• Briefly summarise the development of teeth (primary and permanent)
• Briefly summarise the development of the tongue.
• Know the stages and structures involved in the development of the face.
• Predict the results of abnormal development of the face and palate.

Learning activities

Review the development of endodermal derivatives of the pharynx. Review the development of the face and palate. Review development of pituitary and thyroid. Discuss cleft lip and palate and Pierre Robin Syndrome giving special reference to the development aberrations causing malformations and their consequences.

Computer Activities

UNSW Embryology: Head Abmormalities | Stage 13/14 Head sections | Stage 13/14 (Pig) Overview | Stage 22 Human head sections | Selected Human high power (st22) | Face | Primary Palate | Face Abnormalities | Tongue | Teeth | Skull | Senses | Systems (Pig, pharyngeal) | Head and Neck Sections (Human sets) | Neck (Human sets) | Head Sections (Pig sets)

Embryo Images Unit: Embryo Images Online | Craniofacial Development | Cell Populations | Pharyngeal Arches | Tongue | Nose and Upper Lip | Palate Development

Human Embryology Movies: | Development of the Face (451Kb) | Development of the Tongue (187Kb)

(More? Animations | Movies)

Head and Neck Lectures: ANAT2300 Vertebrate Development- Head Development | ANAM1006 Head Development | ANAT1006 Medicine 2002- Head Development

Pharyngeal Arch Components

Structures derived from Arches, Pouches, Grooves, Membranes

Major features to identify for each: arch, pouch, groove and membrane. Contribute to the formation of head and neck and in the human appear at the 4th week. The first arch contributes the majority of upper and lower jaw structures.

Structures derived from Arches

ARCH	Nerve	Muscles	Skeletal Structures	Ligaments
1 (maxillary/mandibular)	trigeminal (V)		malleus, incus	ant lig of malleus, sphenomandibular ligament
2 (hyoid)	facial (VII)		stapes, styloid process, lesser cornu of hyoid, upper part of body of hyoid bone	stylohyoid ligament
3	glossopharyngeal (IX)		greater cornu of hyoid, lower part of body of hyoid bone
4 & 6	superior laryngeal and recurrent laryngeal branch of vagus (X)		thyroid, cricoid, arytenoid, corniculate and cuneform cartilages

Structures derived from Pouches

Each pouch is lined with endoderm and generates specific structures.

POUCH	Overall Structure	Specific Structures
1	tubotympanic recess	tympanic membrane, tympanic cavity, mastoid antrum, auditory tube
2	intratonsillar cleft	crypts of palatine tonsil, lymphatic nodules of palatine tonsil
3	inferior parathyroid gland, thymus gland
4	superior parathyroid gland, ultimobranchial body
5	becomes part of 4th pouch

Structures derived from Grooves

Only the first groove differentiates into an adult structure and forms part of the external acoustic meatus.

Structures derived from Membranes

At the bottom of each groove lies the membrane which is formed from the contact region of ectodermal groove and endodermal pouch. Only the first membrane differentiates into an adult structure and forms the tympanic membrane.

Development Overview

Early Pharynx and Face Development | Head and Skull | Pharyngeal Arches | Abnormalities | Molecular Mechanisms

Pharynx and Face Early Face and Pharynx Pharynx buccopharyngeal membrane oral membrane apposition of ectoderm with endoderm no mesoderm beween
Head/Skull chondrocranium forms base of skull in lower vertebrates encases brain cranial vault calveria facial skeleton pharyngeal arches Sensory Placodes Head Growth continues postnatally fontanelle allow head distortion on birth and early growth bone plates remain unfused to allow growth puberty growth of face Skull Overview Chondrocranium formed from paraxial mesoderm cranial end of vertebral column modified vertebral elements occipital and cervical sclerotome bone preformed in cartilage endochondrial ossification Cranial Vault and Facial Skeleton formed from neural crest muscle paraxial mesoderm somitomeres and occipital somites Calveria bone has no cartilage direct ossification of mesenchyme bones do not fuse fibrous sutures allow distortion to pass through birth canal allow growth of the brain 6 fontanelles posterior closes at 3 months anterior closes at 18 months
Face derived from pharyngeal or branchial arches Humans have 5 arches 1, 2, 3, 4, 6 Arch 5 does not form or regresses from in rostro-caudal sequence Arch 1->6 week 4 onwards arch 1 and 2 appear at time of closure of cranial neuropore each arch has initially similar components but forms different structures Face mainly arch 1 and 2 Neck components arch 3 and 4 arch 4 and 6 fuse Pharynx and Face Arches Stage 13/14 Embryo
Pharyngeal Arch Development branchial arch (Gk. branchia= gill) arch consists of all 3 trilaminar embryo layers ectoderm- outside mesoderm- core of mesenchyme endoderm- inside Neural Crest Mesenchyme invaded by neural crest generating connective tissue components cartilage, bone, ligaments arises from midbrain and hindbrain region Arch Features Each arch contains artery cartilage nerve muscular component Arches and Phanynx Form face, tongue, lips, jaws, palate, pharynx and neck cranial nerves, sense organ components, glands Arch Features arch groove externally separates each arch also called a cleft only first pair persist as external auditory meatus pouch internally separates each arch pockets from the pharynx membrane ectoderm and endoderm contact regions only first pair persist as tympanic membrane Pharyngeal Arch 1 Mandibular Arch has 2 prominances smaller upper- maxillary forms maxilla, zygomatic bone and squamous part of temporal larger lower- mandibular mandible Pharyngeal Arch 2 Hyoid Arch forms most of hyoid bone Arch 3 and 4 neck structures Arch Arteries placental vein -> liver -> heart -> truncus arteriosus truncus arteriosus -> aortic sac -> each arch artery arch artery -> dorsal aorta -> Arch Arteries Arch 1 mainly lost, form part of maxillary artery Arch 2 stapedial arteries Arch 3 common carotid arteries internal carotid arteries Arch 4 left forms part of aortic arch right forms part right subclavian artery Arch 6 left- part of left pulmonary artery right- part of right pulmonary artery Arch Cartilage Arch 1- Meckel's cartilage dorsal ends form malleus and incus midpart forms ligaments ant. malleus, sphenomandibular ventral part forms mandible template horseshoe shaped Arch 2- Reichert's cartilage dorsal ends form stapes and Temporal bone styloid process ventral part ossifies to form hyoid bone components lesser cornu and superior body Arch 3- forms greater cornu and inferior part of hyoid Arch 4&6- form laryngeal cartilages except epiglottis (from hypobranchial eminence) Arch Muscle Arch 1 muscles of mastication, mylohyoid, tensor tympanic, ant. belly digastric Arch 2 muscles of facial expression, stapedius, stylohyoid, post. belly digastric Arch 3 stylopharyngeus Arch 4&6 crycothyroid, pharynx constrictors, larynx muscles, oesophagus (st. muscle) Arch Nerve Arch 1 CN V trigeminal caudal 2/3 maxillary and mandibular cranial 1/3 sensory nerve of heaad and neck, mastication motor Arch 2 CN VII facial Arch 3 CN IX glossopharyngeal Arch 4&6 CN X vagus arch 4- superior laryngeal arch 6- recurrent laryngeal Arch Pouches Arch 1 elongates to form tubotympanic recess tympanic cavity, mastoid antrum, eustachian tube Arch 2 forms tonsillar sinus mostly oblierated by palatine tonsil Arch 3 forms inferior parathyroid and thymus Arch 4 forms superior parathyroid, parafollicular cells of Thyroid

Thyroid Gland

• Thyroid Gland
• not a pouch structure
• first endocrine organ to develop day 24
• from floor of pharynx
• descends thyroglossal duct (which closes)
• upper end at foramen cecum

Face Development

• begins week 4 centered around stomodeum
• external depression at oral membrane
• 5 initial primordia from neural crest mesenchyme
  • single frontonasal prominence (FNP)
  • forms forehead, nose dorsum and apex
  • nasal placodes develop later bilaterally
  • pushed medially
• paired maxillary prominences
  • form upper cheek and upper lip
• paired mandibular prominences
  • lower cheek, chin and lower lip

Ear Auricles

• form from 6 hillocks (week 5)
• 3 on each of arch 1 and 2

Facial Prominences

Tongue Development

• Contributions from all arches
• which changes with time
• begins as swelling rostral to foramen cecum
• median tongue bud

Arch 1

• oral part of tongue (ant 3/2)

Arch 2

• initial contribution to surface is lost

Arch 3

• pharyngeal part of tongue (post 1/3)

Arch 4

• epiglottis and adjacent regions

Salivary Glands

• epithelial buds in oral cavity (wk 6-7) extend into mesenchyme
• parotid, submandibular, sublingual

Sensory placodes

Sensory placodes

Abnormalities

• First Arch Syndrome
  • 2 major types, both result in extensive facial abnormalites
  • Treacher Collins Syndrome
  • Pierre Robin Syndrome
• DiGeorge Syndrome
  • absence of thymus and parathyroid glands
  • 3rd and 4th pouch do not form
  • disturbance of cervical neural crest migration
• Cysts
  • many different types
• Cleft Lip and Palate
  • 300+ different abnormalities
  • different cleft forms and extent
  • upper lip and ant. maxilla
  • hard and soft palate
• Facial Clefts
  • extremely rare
• Holoprosencephaly
  • shh abnormality
• Maternal Effects
  • Retinoic Acid
    • present in skin ointments
    • 1988 associated with facial developmental abnormalities
    • Abnormalities 4- Maternal Effects
  • Fetal Alcohol Syndrome
    • due to alcohol in early development (week 3+)
    • facial and neurological abnormalities
    • lowered ears, small face, mild+ retardation
      • Microcephaly - leads to small head circumference
      • Short Palpebral fissure - opening of eye
      • Epicanthal folds - fold of skin at inside of corner of eye
      • Flat midface
      • Low nasal bridge
      • Indistinct Philtrum - vertical grooves between nose and mouth
      • Thin upper lip
      • Micrognathia - small jaw
    • exposure of embryos in vitro to ethanol simulates premature differentiation of prechondrogenic mesenchyme of the facial primordia (1999)

Molecular Mechanisms

• Recent experiments with human embryos have shown that gene expression in the head region follows that seen in other species embryo models
• Branchial HOX Gene Expression and Human Craniofacial Development
  • Vieille-Grosjean etal. Dev Biol. 1997
• hindbrain segmentation into rhombomeres
• Hox expression regulates segmentation
• retinoic acid may regulate Hox expression
• Neural Crest migrates into arches from specific rhombomere levels
• Dlx Expression
  • dlx are homeobox genes
  • family of dlx-1 to dlx-7
  • regulates Anterior-Posterior identity
  • dlx-1 and -2 regulate arch 1
• paraxial mesoderm unsegmented somitomeres (7)
• follows neural crest migration pathways
• somitomere 3 mesodermal cells (blue) in Arch 1
• SHH
  • expressed in arches
  • regulates midface formation
• Pax-3 expressed in placode cells
  • contribute to the CNV
  • ophthalmic branch

Development Terms

• anlage- (Ger. ) primordium, structure or cells which will form a future structure.
• brain- general term for the central nervous system formed from 3 primary vesicles.
• buccopharyngeal membrane- (=oral membrane) at cranial (mouth) end of gastrointestinal tract (GIT) where surface ectoderm and GIT endoderm meet. (see also cloacal membrane)
• cloacal membrane- at caudal (anal) end of gastrointestinal tract (GIT) where surface ectoderm and GIT endoderm meet forms the openings for GIT, urinary, reproductive tracts. (see also buccopharyngeal membrane)
• connective tissue-
• dermomyotome- dorsolateral half of each somite that forms the dermis and muscle.
• dorsal root ganglia- (=spinal ganglia) sensory ganglia derived from the neural crest lying laterally paired and dorsally to the spinal cord (in the embryo found ventral to the spinal cord). Connects centrally with the dorsal horn of the spinal cord.
• dura mater-
• ectoderm- the layer (of the 3 germ cell layers) which form the nervous system from the neural tube and neural crest and also generates the epithelia covering the embryo.
• endoderm- the layer (of the 3 germ cell layers) which form the epithelial lining of the gastrointestinal tract (GIT) and accessory organs of GIT in the embryo.
• epiblast- the layer (of the bilaminar embryo) that generates endoderm and mesoderm by migration of cells through the primitive streak. The remaing cells form ectoderm.
• growth factor- usually a protein or peptide that will bind a cell membrane receptor and then activates an intracellular signaling pathway. The function of the pathway will be to alter the cell directly or indirectly by changing gene expression. (eg shh)
• hox- (=homeobox) family of transcription factors that bind DNA and activate gene expression. Expression of different Hox genes along neural tube defines rostral-caudal axis and segmental levels.
• mesoderm- the middle layer of the 3 germ cell layers of the embryo. Mesoderm outside the embryo and covering the amnion, yolk and chorion sacs is extraembryonic mesoderm.
• muscle- 3 main types of muscle (smooth, cardiac and skeletal) all derived from mesoderm but different regions.
• myotome-
• myoblast-
• neural crest- cell region at edge of neural plate, then atop the neural folds, that remains outside and initially dorsal to the neural tube when it forms. These paired dorsal lateral streaks of cells migrate throughout the embryo and can differentiate into many different cell types(=pluripotential). Those that remain on the dorsal neural tube form the sensory spinal ganglia (DRG). Neural crest cells migrate into the somites.
• neural tube- neural plate region of ectoderm pinched off to form hollow ectodermal tube above notochord in mesoderm.
• neuropore- opening at either end of neural tube: cranial=rostral=anterior, caudal=posterior. The cranial neuropore closes (day 25) approx. 2 days (human) before caudal.
• notochord- rod of cells lying in mesoderm layer ventral to the neural tube, induces neural tube and secretes sonic hedgehog which "ventralizes" the neural tube and may influence somite development.
• otocyst- (=otic vesicle) sensory placode which sinks into mesoderm to form spherical vesicle (stage 13/14 embryo) that will form components of the inner ear.
• pharyngeal arches- (=branchial arches, Gk. gill) form structures of the head. Six arches form but only 4 form any structures. Each arch has a pouch, membrane and cleft.
• pharynx- uppermost end of GIT, beginning at the buccopharyngeal membrane and at the level of the pharyngeal arches.
• segmentation-
• spinal cord- caudal end of neural tube that does not contribute to brain. Note: the process of secondary neuralation contributes the caudal end of the spinal cord.
• sonic hedgehog- (=shh) secreted growth factor that binds patched (ptc) receptor on cell membrane. SHH function is different for different tissues in the embryo. In the nervous system, it is secreted by the notochord, ventralizes the neural tube, inducing the floor plate and motor neurons.
• transcription factor- a factor (protein or protein with steroid) that binds to DNA to alter gene expression, usually to activate. (eg steroid hormone+receptor, Retinoic acid+Receptor, Hox, Pax, Lim, Nkx-2.2)

Glossary of Terms

A |B | C | D | E | F | G | H | I | J | K | L | M | N | O | P | Q | R | S | T | U | V | W |X | Y | Z

Quick Links

Head and Neck Pages:

| References | | OMIM | Questions | Medline | Pig Stage 13/14 | Human (Stage22) | Human (stage 22) | Selected Human (stage 22) | Text only page | WWW Links

Development Notes ----------------- Menstrual Cycle Week 1 Week 2 Week 3 Week 4 Placenta Serial Images Genes/DNA Molecular Dev Abnormal Dev Postnatal Dev Notes Index

System Notes ----------------- Heart/Cardiovascular Respiratory Coelomic cavity Gastrointestinal Tract Head and Neck Neural Neural Crest Eye Ear Nose Endocrine Urogenital Musculoskeletal Integumentary

Movies ----------------- Embryo Growth Ultrasound Week 1 Week 2 Week 3 Week 4 Stage 13/14 Stage 22 Neural Head and Neck Heart Vasculature Gastrointestinal Urogenital Other Embryos Larsen Internet

Other Embryos ----------------- Chicken Fly Frog Mouse Rabbit Rat Worm Zebrafish Guinea Pig

UNSW Embryology ISBN: 978 0 7334 2609 4

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