development of the branchial arches

Development of the branchial arches

Heather Etchevers, Ph.D.

INSERM

Arches,arteries, gills

Endoderm Mesenchyme Cardiovascular Pathologies andsummary

Relation of face to pharynx

frontonasalbud

maxillary process

mandibular process

Arches,arteries, gills

Endoderm Mesenchyme Cardiovascular Pathologies andsummary

Pharyngeal arches are also known as branchial or aortic

The embryonic dorsal aortae are paired before later fusing at the midline

Arches,arteries, gills

Endoderm Mesenchyme Cardiovascular Pathologies andsummary

Pharyngeal arches The arches are metameric structures numbered 1 to

4 and 6 in humans “#5” does not exist as a separate entity

Each arch is built around the cage of aortic arches between ventral and dorsal aortae

Each pair = unique complement of: Muscles and connective tissue Nerves Cartilage (bone for PA1-3) Segment of the branchial arterial tree Endodermal anlage to the neck glands

Arches,arteries, gills

Endoderm Mesenchyme Cardiovascular Pathologies andsummary

The first aortic arch is the precursor to all pharyngeal arches

Ventral view, human embryonic heart

Arches,arteries, gills

Endoderm Mesenchyme Cardiovascular Pathologies andsummary

Rostrocaudal maturation of arches

Detrait and Etchevers, 2005

Arches,arteries, gills

Endoderm Mesenchyme Cardiovascular Pathologies andsummary

All pharyngeal arch arteries are never present at once

Obliterated1st PA

Maxillaryartery

Right dorsal aorta

Left dorsal aorta

1st PA

2nd PA

3rd PA

4th PA

Constant remodelingduring embryonic life

Growth factor guidance of endothelial cells

Immature mural coverage

Flow pressures and hemodynamics

Arches,arteries, gills

Endoderm Mesenchyme Cardiovascular Pathologies andsummary

Craniofacial evolutionfrontaleye

cerebral vesicle

Amphioxus

MOUTH

selection of NCC

retina

Lampreypros

MOUTH

mes

retina

selection of NCC

Gnathostome

MOUTH

pros

mes

MOUTH

MOUTH

Arches,arteries, gills

Endoderm Mesenchyme Cardiovascular Pathologies andsummary

Volumes and surfaces Outer, notched

ectoderm Inner, pouched-out

endoderm Membranes where they

meet Mesodermal core of

muscle and vascular endothelium

Neural crest mesenchyme

hindbrain

prosPA1

2 3

4

heart

Arches,arteries, gills

Endoderm Mesenchyme Cardiovascular Pathologies andsummary

Pouches and grooves

1

2

Persists astympanicmembrane

endodermectoderm

Persists asintratonsillarcleft

bpm

midbrain

3

Arches,arteries, gills

Endoderm Mesenchyme Cardiovascular Pathologies andsummary

Endoderm and vascular development

Dorsal aorta

Arterial vitellineplexus

Endoderm

1st pharyngeal pouch

Vitelline arteries

Pharyngeal arch arteries

Internal carotid

Umbilical arteries

Arches,arteries, gills

Endoderm Mesenchyme Cardiovascular Pathologies andsummary

Endodermal expression of hypoxia-inducible factor 1

HIF1 is a TF activated under hypoxic/growth conditions

It effects transcription of pro-vascular factors such as VEGF, ET-1

Etchevers, 2003

Arches,arteries, gills

Endoderm Mesenchyme Cardiovascular Pathologies andsummary

Endodermal derivatives of pouches

Pharyngealendoderm

Derivative

1 Epithelium of tympanic cavity and auditory tube

2 Epithelium of tonsil

3 Inferior parathyroid glands and epithelium of thymus

4 Superior parathyroid glands

Arches,arteries, gills

Endoderm Mesenchyme Cardiovascular Pathologies andsummary

Arches,arteries, gills

Endoderm Mesenchyme Cardiovascular Pathologies andsummary

Tongue and salivary glands Contributions from most arches Endoderm and mesoderm First

oral anterior 2/3 Second

Surface contribution not maintained; tonsillar crypts Third

pharyngeal posterior 1/3 Fourth

Epiglottis and vicinity The salivary glands are ectodermal ingrowths of the

oral cavity that associate with NC mesenchyme

Arches,arteries, gills

Endoderm Mesenchyme Cardiovascular Pathologies andsummary

Structural derivativesPharyngeal Arch Cranial Nerve Muscle derivative Skeletal Derivative

1Maxillary

Trigeminal nerve (V) Superior obliqueAbducensOculomotor muscles

Maxillary, palatine, jugaltrabecula cranii

1Mandibular

Trigeminal nerve (V) Muscles of masticationTensor tympanisDigastric (anterior belly)

Incus, ant. lig of malleuspalatoquadrateMeckel’s cartilage

2 Hyoid

Facial nerve (VII) Muscles of facial expression, digastric (posterior belly), styloid

Stapes, hyoid boneReichert’s cartilage

3 Glossopharyngeal nerve (IX)

stylopharyngeas Horns of hyoidThyroid cartilage

4 and 6 Laryngeal branches of vagus nerve (X)

Striated muscles of oesophagus

Cricoid cartilage

Arches,arteries, gills

Endoderm Mesenchyme Cardiovascular Pathologies andsummary

Cartilage derivatives of arches in 24 wk foetus

Arches,arteries, gills

Endoderm Mesenchyme Cardiovascular Pathologies andsummary

Hox segment identity genes are incompatible with facial skeleton

Creuzet et al. (2002)Couly et al. 1993

Arches,arteries, gills

Endoderm Mesenchyme Cardiovascular Pathologies andsummary

Human embryo aortic arches

Courtesy of Next Generation Embryologyhttp://ngembryo.ncl.ac.uk/ngembryo.php

Arches,arteries, gills

Endoderm Mesenchyme Cardiovascular Pathologies andsummary

Chicken head vessels are in two sectors

Arches,arteries, gills

Endoderm Mesenchyme Cardiovascular Pathologies andsummary

Vascular derivatives

Pharyngeal arch Arteries Veins-tentative

1st maxillary (shared artery with mandibular)

Ophthalmic, ethmoid, ramus superior of stapedial

1st mandibular Maxillary, mandibular

2nd hyoid Stapedial

3rd Common and internal carotids

4th Right subclavian (R)Aorta (L)

6th Right proximal pulmonaryLeft proximal pulmonaryDuctus arteriosis

Internal/ external jugular

BrachiocephalicSubclavian

Sinus venosus?

Arches,arteries, gills

Endoderm Mesenchyme Cardiovascular Pathologies andsummary

The “cardiac” neural crest is a subpopulation of the cephalic crest

Arches,arteries, gills

Endoderm Mesenchyme Cardiovascular Pathologies andsummary

Heart participation of NCC is necessary but transitory

© K Sulik and coll.

Arches,arteries, gills

Endoderm Mesenchyme Cardiovascular Pathologies andsummary

Oculo-auriculo-vertebral spectrum

a.k.a. First arch or Goldenhar syndrome, hemifacial microsomia – though can be bilateral

Malformation of jaws, ears and face Experimentally induced by hemorrhage of 2nd

pharyngeal arch Fortuitous genetic mouse model Often overlaps with DiGeorge, VACTERL…

Arches,arteries, gills

Endoderm Mesenchyme Cardiovascular Pathologies andsummary

Goldenhar, First arch, hemifacial microsomia, oculo-auriculo-vertebral spectrum (MIM 164210)

Axial 1-mm 3D FT-CISS MR image through temporal bones. Lemmerling et al., AJNR 2000.

semi-circularcanals(L)

enlargedvestibularaqueduct(R)

Universitätsklinikum Jena

Arches,arteries, gills

Endoderm Mesenchyme Cardiovascular Pathologies andsummary

Cardiovascular defects in DGS

Arches,arteries, gills

Endoderm Mesenchyme Cardiovascular Pathologies andsummary

Congenital vascular anomalies arise from defective arch remodeling Double aortic arch

Non-regression of right aortic arch

Aberrant right subclavian artery 1% of normal population but 40% of tri 21 or CHD

Right aortic arch Retention of the dorsal aorta on right side Ductus arteriosus deflected to right Up to 1/3 of tetralogy of Fallot, 1/10 TGV

Interrupted aortic arch Regression of both right and left 4th arch

Coarctation of aorta Constriction near normally remodeling ductus arteriosus (6th

arch)

Arches,arteries, gills

Endoderm Mesenchyme Cardiovascular Pathologies andsummary

Main points

Pharyngeal arches are metameric structures They each contain all germ layers, each of

which contributes to distinct structures for each arch

Hox genes confer identity to differentiate them like for other metameric structures (eg. somites) not with respect to the facial skeleton

Arch, facial and heart development are linked