UNSW Embryology

Head and Neck Development- Face

© Dr Mark Hill (2008)

Acknowledgements

Introduction

This page introduces the topic of face formation and links to a series of pages covering normal and abnormal development during the embryonic and fetal period.

(Carnegie stage 16 to 18, Kyoto collection)

(More? Face Development 16 to 18)

Page Links: Introduction | Some Recent Findings | Reading | Development Overview | Serial Images | Abnormalities |WWW Links | References | Glossary

Some Recent Findings

Kurjak A, Azumendi G, Andonotopo W, Salihagic-Kadic A. Three- and four-dimensional ultrasonography for the structural and functional evaluation of the fetal face. Am J Obstet Gynecol. 2007 Jan;196(1):16-28. Epub 2006 Oct 2. Review.

Brito JM, Teillet MA, Le Douarin NM. An early role for Sonic hedgehog from foregut endoderm in jaw development: Ensuring neural crest cell survival. Proc Natl Acad Sci U S A. 2006 Aug 1;103(31):11607-12. Epub 2006 Jul 25.

Experiments in chicken show "Shh derived from the ventral foregut endoderm ensures the survival of neural crest cells at a critical stage of first branchial arch (BA1) development."

Developmental Dynamics Special Issue: Craniofacial Development Special Issue Volume 235 Issue 5 - May 2006 (1151 - 1454)

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.

"Ectodermal placodes comprise the adenohypophyseal, olfactory, lens, profundal, trigeminal, otic, lateral line, and epibranchial placodes. ...A scenario is presented according to which all placodes evolved from an adenohypophyseal-olfactory protoplacode, which may have originated in the vertebrate ancestor from the anlage of a rostral neurosecretory organ (surviving as Hatschek's pit in present-day amphioxus)."

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.

"...our results indicate that the Hh signaling pathway is critical to Meckel's cartilage ontogenesis and the rate of chondrogenesis, but not to initial primordium formation."

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.

Human Embryo Face

Human Embryo Face (Carnegie stage 16 to 18, Kyoto collection)

(More? Face Development cartoon)

Objectives

Historic images comparing face formation in different species.

Reading

Diewert VM, Wang KY. Recent advances in primary palate and midface morphogenesis research. Crit Rev Oral Biol Med. 1992;4(1):111-30. Review.

Diewert VM. Growth movements during prenatal development of human facial morphology. Prog Clin Biol Res. 1985;187:57-66. Review.

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

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

Computer Activities

Embryo Images Unit:

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

Human Embryology Movies:

Development of the Face (451Kb)

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

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

UNSW CRICOS Provider Code No. 00098G