Branchial Apparatus and Aortic Arches

Review of Early Embryologic Development

Blastocyst Blastocyst A post-morula preimplantation mammalian embryo that develops from a 32-cell stage into a fluid-filled hollow ball of over a hundred cells. A blastocyst has two distinctive tissues. The outer layer of trophoblasts gives rise to extra-embryonic tissues. The inner cell mass gives rise to the embryonic disc and eventual embryo proper. Fertilization and First Week and bilaminar disc Bilaminar disc Embryoblast and Trophoblast Development

The morula Morula An early embryo that is a compact mass of about 16 blastomeres. It resembles a cluster of mulberries with two types of cells, outer cells and inner cells. Morula is the stage before blastula in non-mammalian animals or a blastocyst in mammals. Fertilization and First Week (ball of cells) undergoes a process called blastulation, in which a cavity begins to form. The cells then begin differentiating into outer and inner cell masses.

• Outer cell mass Mass Three-dimensional lesion that occupies a space within the breast Imaging of the Breast → trophoblast Trophoblast Cells lining the outside of the blastocyst. After binding to the endometrium, trophoblasts develop into two distinct layers, an inner layer of mononuclear cytotrophoblasts and an outer layer of continuous multinuclear cytoplasm, the syncytiotrophoblasts, which form the early fetal-maternal interface (placenta). Fertilization and First Week → placenta Placenta A highly vascularized mammalian fetal-maternal organ and major site of transport of oxygen, nutrients, and fetal waste products. It includes a fetal portion (chorionic villi) derived from trophoblasts and a maternal portion (decidua) derived from the uterine endometrium. The placenta produces an array of steroid, protein and peptide hormones (placental hormones). Placenta, Umbilical Cord, and Amniotic Cavity and membranes
• Inner cell mass Mass Three-dimensional lesion that occupies a space within the breast Imaging of the Breast → embryoblast Embryoblast Embryoblast and Trophoblast Development → bilaminar disc Bilaminar disc Embryoblast and Trophoblast Development:
  • Epiblast Epiblast Embryoblast and Trophoblast Development
  • Hypoblast Hypoblast Embryoblast and Trophoblast Development
• Amniotic sac: cavity of fluid that develops “above” the epiblast Epiblast Embryoblast and Trophoblast Development (between epiblast Epiblast Embryoblast and Trophoblast Development and trophoblast Trophoblast Cells lining the outside of the blastocyst. After binding to the endometrium, trophoblasts develop into two distinct layers, an inner layer of mononuclear cytotrophoblasts and an outer layer of continuous multinuclear cytoplasm, the syncytiotrophoblasts, which form the early fetal-maternal interface (placenta). Fertilization and First Week)
• Primitive yolk sac Yolk Sac The first of four extra-embryonic membranes to form during embryogenesis. In reptiles and birds, it arises from endoderm and mesoderm to incorporate the egg yolk into the digestive tract for nourishing the embryo. In placental mammals, its nutritional function is vestigial; however, it is the source of intestinal mucosa; blood cells; and germ cells. It is sometimes called the vitelline sac, which should not be confused with the vitelline membrane of the egg. Embryoblast and Trophoblast Development: cavity that forms “below” the hypoblast Hypoblast Embryoblast and Trophoblast Development (between hypoblast Hypoblast Embryoblast and Trophoblast Development and trophoblast Trophoblast Cells lining the outside of the blastocyst. After binding to the endometrium, trophoblasts develop into two distinct layers, an inner layer of mononuclear cytotrophoblasts and an outer layer of continuous multinuclear cytoplasm, the syncytiotrophoblasts, which form the early fetal-maternal interface (placenta). Fertilization and First Week)

Trilaminar disc Trilaminar disc Gastrulation and Neurulation

The bilaminar disk undergoes a process called gastrulation Gastrulation Both gastrulation and neurulation are critical events that occur during the 3rd week of embryonic development. Gastrulation is the process by which the bilaminar disc differentiates into a trilaminar disc, made up of the 3 primary germ layers: the ectoderm, mesoderm, and endoderm. Gastrulation and Neurulation to form the trilaminar disc Trilaminar disc Gastrulation and Neurulation. Cells from the epiblast Epiblast Embryoblast and Trophoblast Development layer migrate downward, replacing the hypoblast Hypoblast Embryoblast and Trophoblast Development ( endoderm Endoderm The inner of the three germ layers of an embryo. Gastrulation and Neurulation) and creating a 3rd layer in between ( mesoderm Mesoderm The middle germ layer of an embryo derived from three paired mesenchymal aggregates along the neural tube. Gastrulation and Neurulation). 

• Ectoderm Ectoderm The outer of the three germ layers of an embryo. Gastrulation and Neurulation (dorsal layer):
  • Continuous with the amnion Amnion The innermost membranous sac that surrounds and protects the developing embryo which is bathed in the amniotic fluid. Amnion cells are secretory epithelial cells and contribute to the amniotic fluid. Placenta, Umbilical Cord, and Amniotic Cavity 
  • Formed from cells remaining in the epiblast Epiblast Embryoblast and Trophoblast Development layer
  • Ectoderm-derived structures:
    • Neural tube Neural tube A tube of ectodermal tissue in an embryo that will give rise to the central nervous system, including the spinal cord and the brain. Lumen within the neural tube is called neural canal which gives rise to the central canal of the spinal cord and the ventricles of the brain. Gastrulation and Neurulation → brain Brain The part of central nervous system that is contained within the skull (cranium). Arising from the neural tube, the embryonic brain is comprised of three major parts including prosencephalon (the forebrain); mesencephalon (the midbrain); and rhombencephalon (the hindbrain). The developed brain consists of cerebrum; cerebellum; and other structures in the brain stem. Nervous System: Anatomy, Structure, and Classification and spinal cord Spinal cord The spinal cord is the major conduction pathway connecting the brain to the body; it is part of the CNS. In cross section, the spinal cord is divided into an H-shaped area of gray matter (consisting of synapsing neuronal cell bodies) and a surrounding area of white matter (consisting of ascending and descending tracts of myelinated axons). Spinal Cord: Anatomy
    • Neural crest cells Neural crest cells Gastrulation and Neurulation → cranial nerves Cranial nerves There are 12 pairs of cranial nerves (CNs), which run from the brain to various parts of the head, neck, and trunk. The CNs can be sensory or motor or both. The CNs are named and numbered in Roman numerals according to their location, from the front to the back of the brain. The 12 Cranial Nerves: Overview and Functions associated with the branchial arches, PNS
• Mesoderm Mesoderm The middle germ layer of an embryo derived from three paired mesenchymal aggregates along the neural tube. Gastrulation and Neurulation (middle layer) has several components:
  • Paraxial mesoderm Mesoderm The middle germ layer of an embryo derived from three paired mesenchymal aggregates along the neural tube. Gastrulation and Neurulation → forms the mesodermal component of the branchial arches
  • Intermediate mesoderm Intermediate mesoderm Development of the Urogenital System → genitourinary system
  • Lateral plate mesoderm Mesoderm The middle germ layer of an embryo derived from three paired mesenchymal aggregates along the neural tube. Gastrulation and Neurulation (LPM):
    • Somatic layer of the LPM Somatic layer of the LPM Development of the Abdominal Organs 
    • Splanchnic layer of the LPM Splanchnic layer of the LPM Development of the Abdominal Organs → forms primitive heart tube and pharyngeal aortic arches
  • Extraembryonic mesoderm Extraembryonic mesoderm Embryoblast and Trophoblast Development:
    • Surrounds the amniotic cavity Amniotic cavity Embryoblast and Trophoblast Development → continuous with somatic LPM
    • Surrounds the yolk sac Yolk Sac The first of four extra-embryonic membranes to form during embryogenesis. In reptiles and birds, it arises from endoderm and mesoderm to incorporate the egg yolk into the digestive tract for nourishing the embryo. In placental mammals, its nutritional function is vestigial; however, it is the source of intestinal mucosa; blood cells; and germ cells. It is sometimes called the vitelline sac, which should not be confused with the vitelline membrane of the egg. Embryoblast and Trophoblast Development → continuous with splanchnic LPM
• Endoderm Endoderm The inner of the three germ layers of an embryo. Gastrulation and Neurulation (ventral layer):
  • Embryonic endoderm Endoderm The inner of the three germ layers of an embryo. Gastrulation and Neurulation (usually just called the endoderm Endoderm The inner of the three germ layers of an embryo. Gastrulation and Neurulation) → becomes the primitive gut tube → most GI organs
  • Extraembryonic endoderm Endoderm The inner of the three germ layers of an embryo. Gastrulation and Neurulation → lines the yolk sac Yolk Sac The first of four extra-embryonic membranes to form during embryogenesis. In reptiles and birds, it arises from endoderm and mesoderm to incorporate the egg yolk into the digestive tract for nourishing the embryo. In placental mammals, its nutritional function is vestigial; however, it is the source of intestinal mucosa; blood cells; and germ cells. It is sometimes called the vitelline sac, which should not be confused with the vitelline membrane of the egg. Embryoblast and Trophoblast Development
• Folding of the trilaminar disk (folds in 2 directions):
  • Lateral folding:
    • Creates a cylindrical structure surrounded by ectoderm Ectoderm The outer of the three germ layers of an embryo. Gastrulation and Neurulation and amniotic cavity Amniotic cavity Embryoblast and Trophoblast Development
    • Creates primitive gut tube internally from endoderm Endoderm The inner of the three germ layers of an embryo. Gastrulation and Neurulation
  • Cranial–caudal folding:
    • Creates a cranial end and a caudal end ( embryo Embryo The entity of a developing mammal, generally from the cleavage of a zygote to the end of embryonic differentiation of basic structures. For the human embryo, this represents the first two months of intrauterine development preceding the stages of the fetus. Fertilization and First Week becomes bean-shaped)
    • Forces the yolk sac Yolk Sac The first of four extra-embryonic membranes to form during embryogenesis. In reptiles and birds, it arises from endoderm and mesoderm to incorporate the egg yolk into the digestive tract for nourishing the embryo. In placental mammals, its nutritional function is vestigial; however, it is the source of intestinal mucosa; blood cells; and germ cells. It is sometimes called the vitelline sac, which should not be confused with the vitelline membrane of the egg. Embryoblast and Trophoblast Development farther from the body. The elongating stalk connecting the yolk sac Yolk Sac The first of four extra-embryonic membranes to form during embryogenesis. In reptiles and birds, it arises from endoderm and mesoderm to incorporate the egg yolk into the digestive tract for nourishing the embryo. In placental mammals, its nutritional function is vestigial; however, it is the source of intestinal mucosa; blood cells; and germ cells. It is sometimes called the vitelline sac, which should not be confused with the vitelline membrane of the egg. Embryoblast and Trophoblast Development to the gut tube is the vitelline duct Vitelline duct The narrow tube connecting the yolk sac with the midgut of the embryo; persistence of all or part of it in post-fetal life produces abnormalities, of which the commonest is meckel diverticulum. Meckel’s Diverticulum.

Origin and Structure of the Branchial Apparatus

Development of the branchial apparatus

The branchial (meaning “gills”) apparatus is also known as the pharyngeal apparatus in humans.

• Occurs in the 4th–5th embryonic week
• In humans, 5 arch-shaped bulges or folds form off the ventral side of the foregut Foregut Development of the Abdominal Organs (part of the primitive gut tube) in the region that will become the head and neck Neck The part of a human or animal body connecting the head to the rest of the body. Peritonsillar Abscess.
  • Named branchial arches I–VI
    • Arches I, II, III, IV, and VI exist in humans
    • Arch V does not exist in humans; it is a structure in other vertebrates (e.g., fish FISH A type of in situ hybridization in which target sequences are stained with fluorescent dye so their location and size can be determined using fluorescence microscopy. This staining is sufficiently distinct that the hybridization signal can be seen both in metaphase spreads and in interphase nuclei. Chromosome Testing).
    • 4th and 6th arches fuse → results in 4 total pharyngeal arches
  • Each of the arches consists of all 3 germ layers:
    • Endoderm Endoderm The inner of the three germ layers of an embryo. Gastrulation and Neurulation: internal layer
    • Mesoderm Mesoderm The middle germ layer of an embryo derived from three paired mesenchymal aggregates along the neural tube. Gastrulation and Neurulation: central core
    • Ectoderm Ectoderm The outer of the three germ layers of an embryo. Gastrulation and Neurulation: external layer
• Mesenchymal cells migrate downward (ventrally) from the paraxial mesoderm Mesoderm The middle germ layer of an embryo derived from three paired mesenchymal aggregates along the neural tube. Gastrulation and Neurulation, surrounding the endoderm-derived foregut Foregut Development of the Abdominal Organs:
  • Form the lateral wall of the digestive tract 
  • Continue to proliferate in the cranial portion of the tube forming the mesodermal core of the branchial arches
• Associated with each arch is:
  • A cranial nerve (nerve supply)
  • A pharyngeal aortic arch Aortic arch Mediastinum and Great Vessels: Anatomy (blood supply)
• Arches are separated:
  • Externally by pharyngeal clefts, also called pharyngeal grooves:
    • Made from indentations of ectoderm Ectoderm The outer of the three germ layers of an embryo. Gastrulation and Neurulation
    • Groove/cleft I is below arch I.
  • Internally by pharyngeal pouches
    • Made from indentations of endoderm Endoderm The inner of the three germ layers of an embryo. Gastrulation and Neurulation, directly across from the grooves
    • Pouch I is below arch I.
• Different segments of the tube have different patterns of gene Gene A category of nucleic acid sequences that function as units of heredity and which code for the basic instructions for the development, reproduction, and maintenance of organisms. Basic Terms of Genetics expression → triggers various differentiations of each groove/arch/pouch

Structure and derivatives of the branchial apparatus

• Pharyngeal clefts (also called pharyngeal grooves):
  • 4 indentations of ectoderm Ectoderm The outer of the three germ layers of an embryo. Gastrulation and Neurulation located on the external surface of the structure
  • Becomes external epithelium Epithelium The epithelium is a complex of specialized cellular organizations arranged into sheets and lining cavities and covering the surfaces of the body. The cells exhibit polarity, having an apical and a basal pole. Structures important for the epithelial integrity and function involve the basement membrane, the semipermeable sheet on which the cells rest, and interdigitations, as well as cellular junctions. Surface Epithelium: Histology 
• Pharyngeal arches:
  • 4 cores of mesoderm Mesoderm The middle germ layer of an embryo derived from three paired mesenchymal aggregates along the neural tube. Gastrulation and Neurulation located in the middle of the structure
  • Become:
    • Cartilage Cartilage Cartilage is a type of connective tissue derived from embryonic mesenchyme that is responsible for structural support, resilience, and the smoothness of physical actions. Perichondrium (connective tissue membrane surrounding cartilage) compensates for the absence of vasculature in cartilage by providing nutrition and support. Cartilage: Histology and connective tissue Connective tissue Connective tissues originate from embryonic mesenchyme and are present throughout the body except inside the brain and spinal cord. The main function of connective tissues is to provide structural support to organs. Connective tissues consist of cells and an extracellular matrix. Connective Tissue: Histology
    • Muscle
    • Bones
  • Also contain:
    • Nerves
    • Arteries Arteries Arteries are tubular collections of cells that transport oxygenated blood and nutrients from the heart to the tissues of the body. The blood passes through the arteries in order of decreasing luminal diameter, starting in the largest artery (the aorta) and ending in the small arterioles. Arteries are classified into 3 types: large elastic arteries, medium muscular arteries, and small arteries and arterioles. Arteries: Histology
• Pharyngeal pouches:
  • 4 indentations of endoderm Endoderm The inner of the three germ layers of an embryo. Gastrulation and Neurulation located on the internal surface of the structure
  • Become:
    • Internal epithelium Epithelium The epithelium is a complex of specialized cellular organizations arranged into sheets and lining cavities and covering the surfaces of the body. The cells exhibit polarity, having an apical and a basal pole. Structures important for the epithelial integrity and function involve the basement membrane, the semipermeable sheet on which the cells rest, and interdigitations, as well as cellular junctions. Surface Epithelium: Histology
    • Glands

Development of the Pharyngeal Arches

Development of the pharyngeal arches

The pharyngeal arches develop into key components of the head and neck Neck The part of a human or animal body connecting the head to the rest of the body. Peritonsillar Abscess.

• Each arch contains a core of dense mesenchyme that develops into:
  • Cartilage Cartilage Cartilage is a type of connective tissue derived from embryonic mesenchyme that is responsible for structural support, resilience, and the smoothness of physical actions. Perichondrium (connective tissue membrane surrounding cartilage) compensates for the absence of vasculature in cartilage by providing nutrition and support. Cartilage: Histology rod → bone Bone Bone is a compact type of hardened connective tissue composed of bone cells, membranes, an extracellular mineralized matrix, and central bone marrow. The 2 primary types of bone are compact and spongy. Bones: Structure and Types via endochondral ossification Ossification The process of bone formation. Histogenesis of bone including ossification. Bones: Development and Ossification
  • Muscles
  • Connective tissue Connective tissue Connective tissues originate from embryonic mesenchyme and are present throughout the body except inside the brain and spinal cord. The main function of connective tissues is to provide structural support to organs. Connective tissues consist of cells and an extracellular matrix. Connective Tissue: Histology
• Somitomeres:
  • Segmented muscular tissue from paraxial mesoderm Mesoderm The middle germ layer of an embryo derived from three paired mesenchymal aggregates along the neural tube. Gastrulation and Neurulation located on either side of the neural tube Neural tube A tube of ectodermal tissue in an embryo that will give rise to the central nervous system, including the spinal cord and the brain. Lumen within the neural tube is called neural canal which gives rise to the central canal of the spinal cord and the ventricles of the brain. Gastrulation and Neurulation
  • Migrate into the developing arches
  • Associate with developing cartilage Cartilage Cartilage is a type of connective tissue derived from embryonic mesenchyme that is responsible for structural support, resilience, and the smoothness of physical actions. Perichondrium (connective tissue membrane surrounding cartilage) compensates for the absence of vasculature in cartilage by providing nutrition and support. Cartilage: Histology there
• Branchial nerves:
  • Derived from neural crest cells Neural crest cells Gastrulation and Neurulation, which are originally located dorsal to the neural tube Neural tube A tube of ectodermal tissue in an embryo that will give rise to the central nervous system, including the spinal cord and the brain. Lumen within the neural tube is called neural canal which gives rise to the central canal of the spinal cord and the ventricles of the brain. Gastrulation and Neurulation
  • Migrate with the somitomeres down into the developing mesenchymal tissue of the pharyngeal arches
  • Develop into the cranial nerves Cranial nerves There are 12 pairs of cranial nerves (CNs), which run from the brain to various parts of the head, neck, and trunk. The CNs can be sensory or motor or both. The CNs are named and numbered in Roman numerals according to their location, from the front to the back of the brain. The 12 Cranial Nerves: Overview and Functions innervating the muscles simultaneously developing within each arch
• Blood supply is via the associated branchial aortic arches.

Derivations and associations of each pharyngeal arch

Pharyngeal Aortic Arches

Each branchial arch has its own pair of branchial arch arteries Arteries Arteries are tubular collections of cells that transport oxygenated blood and nutrients from the heart to the tissues of the body. The blood passes through the arteries in order of decreasing luminal diameter, starting in the largest artery (the aorta) and ending in the small arterioles. Arteries are classified into 3 types: large elastic arteries, medium muscular arteries, and small arteries and arterioles. Arteries: Histology; there are 5 aortic arches in humans.

Early development

• Primitive heart tube forms from the splanchnic layer of the LPM Splanchnic layer of the LPM Development of the Abdominal Organs in the first 3 weeks of development.
• Vasculogenesis causes the superior portion of the primitive heart tube to split into:
  • Pulmonary trunk Pulmonary Trunk Truncus Arteriosus
  • Aortic sac
• Pharyngeal aortic arches:
  • Originate as paired vessels from the aortic sac 
  • Wrap around the developing gut tube
  • Lead into the 2 paired dorsal aortas running longitudinally along the embryo Embryo The entity of a developing mammal, generally from the cleavage of a zygote to the end of embryonic differentiation of basic structures. For the human embryo, this represents the first two months of intrauterine development preceding the stages of the fetus. Fertilization and First Week (dorsal aortas merge caudally into the descending aorta Descending aorta Mediastinum and Great Vessels: Anatomy)
• A total of 5 pairs of arches develop in humans:
  • The most cranial arches develop 1st (and regress)
  • Caudal arches develop later

Pharyngeal aortic arch Aortic arch Mediastinum and Great Vessels: Anatomy derivatives

• 1st and 2nd aortic arches: mostly regress
  • 1st arch → maxillary artery
  • 2nd arch → stapedial artery (often degenerates completely, persists in a minority of individuals)
• 3rd aortic arch Aortic arch Mediastinum and Great Vessels: Anatomy: common and internal carotid arteries Carotid Arteries Either of the two principal arteries on both sides of the neck that supply blood to the head and neck; each divides into two branches, the internal carotid artery and the external carotid artery. Carotid Arterial System: Anatomy:
• 4th aortic arch Aortic arch Mediastinum and Great Vessels: Anatomy:
  • Left → the defined aortic arch Aortic arch Mediastinum and Great Vessels: Anatomy
  • Right → proximal section of the right subclavian artery
• 5th aortic arch Aortic arch Mediastinum and Great Vessels: Anatomy: does not develop in humans
• 6th aortic arch Aortic arch Mediastinum and Great Vessels: Anatomy: pulmonary arch
  • Left:
    • Left pulmonary artery Pulmonary artery The short wide vessel arising from the conus arteriosus of the right ventricle and conveying unaerated blood to the lungs. Lungs: Anatomy
    • Ductus arteriosus Ductus arteriosus A fetal blood vessel connecting the pulmonary artery with the descending aorta. Patent Ductus Arteriosus (PDA) 
  • Right:
    • Pulmonary trunk Pulmonary Trunk Truncus Arteriosus 
    • Right pulmonary artery Pulmonary artery The short wide vessel arising from the conus arteriosus of the right ventricle and conveying unaerated blood to the lungs. Lungs: Anatomy

Development of the Pharyngeal Clefts and Pouches

Pharyngeal clefts (pharyngeal grooves)

The pharyngeal clefts are created by the invaginations of ectoderm Ectoderm The outer of the three germ layers of an embryo. Gastrulation and Neurulation on the external between the pharyngeal arches.

• Only 1 of the 4 ectodermal pharyngeal clefts develops into a definite organ system.
• 1st pharyngeal cleft becomes:
  • External auditory canal External Auditory Canal Otitis Externa
  • External surface of the tympanic membrane Tympanic membrane An oval semitransparent membrane separating the external ear canal from the tympanic cavity. It contains three layers: the skin of the external ear canal; the core of radially and circularly arranged collagen fibers; and the mucosa of the middle ear. Ear: Anatomy
• 2nd pharyngeal cleft:
  • Proliferates and grows caudally
  • Grows “over” the 3rd and 4th pharyngeal clefts
  • Merges with the epicardial ridge → forms the cervical sinus (lined by ectoderm Ectoderm The outer of the three germ layers of an embryo. Gastrulation and Neurulation):
    • Later degenerates 
    • If degeneration fails, lateral branchial cleft cysts Cysts Any fluid-filled closed cavity or sac that is lined by an epithelium. Cysts can be of normal, abnormal, non-neoplastic, or neoplastic tissues. Fibrocystic Change may develop.
• 3rd and 4th pharyngeal clefts:
  • Form the medial lining of the cervical sinus
  • Ultimately degenerate

Development of the Pharyngeal Pouches

The pharyngeal pouches are created by the outward folding of endoderm Endoderm The inner of the three germ layers of an embryo. Gastrulation and Neurulation between the pharyngeal arches.

• 1st pharyngeal pouch:
  • Tympanic cavity Tympanic cavity Ear: Anatomy (i.e., middle ear cavity Middle ear cavity Ear: Anatomy)
  • Auditory or eustachian tube Eustachian tube A narrow passageway that connects the upper part of the throat to the tympanic cavity. Ear: Anatomy (draining the middle ear Middle ear The space and structures directly internal to the tympanic membrane and external to the inner ear (labyrinth). Its major components include the auditory ossicles and the eustachian tube that connects the cavity of middle ear (tympanic cavity) to the upper part of the throat. Acute Otitis Media into the nasal cavity Nasal cavity The proximal portion of the respiratory passages on either side of the nasal septum. Nasal cavities, extending from the nares to the nasopharynx, are lined with ciliated nasal mucosa. Nose Anatomy (External & Internal))
• 2nd pharyngeal pouch: tonsils Tonsils Tonsillitis
• 3rd pharyngeal pouch: splits into dorsal and ventral components:
  • Dorsal sprout → inferior parathyroid Parathyroid The parathyroid glands are 2 pairs of small endocrine glands found in close proximity to the thyroid gland. The superior parathyroid glands are lodged within the parenchyma of the upper poles of the right and left thyroid lobes; the inferior parathyroid glands are close to the inferior tips or poles of the lobes. Parathyroid Glands: Anatomy glands (start higher and move down)
  • Ventral sprout → thymus Thymus A single, unpaired primary lymphoid organ situated in the mediastinum, extending superiorly into the neck to the lower edge of the thyroid gland and inferiorly to the fourth costal cartilage. It is necessary for normal development of immunologic function early in life. By puberty, it begins to involute and much of the tissue is replaced by fat. Lymphatic Drainage System: Anatomy (starts in the neck Neck The part of a human or animal body connecting the head to the rest of the body. Peritonsillar Abscess and moves down into the chest)
• 4th pharyngeal pouch: splits into dorsal and ventral components:
  • Dorsal sprout → superior parathyroid Parathyroid The parathyroid glands are 2 pairs of small endocrine glands found in close proximity to the thyroid gland. The superior parathyroid glands are lodged within the parenchyma of the upper poles of the right and left thyroid lobes; the inferior parathyroid glands are close to the inferior tips or poles of the lobes. Parathyroid Glands: Anatomy glands (start lower and move up)
  • Ventral sprout → ultimobranchial body (sometimes attributed to a 5th pharyngeal pouch) → calcitonin-producing parafollicular or C cells C cells Calcium Hemostasis and Bone Metabolism of the thyroid Thyroid The thyroid gland is one of the largest endocrine glands in the human body. The thyroid gland is a highly vascular, brownish-red gland located in the visceral compartment of the anterior region of the neck. Thyroid Gland: Anatomy gland

Clinical Relevance

1st and 2nd arch syndromes

• Treacher-Collins syndrome: underdevelopment of the jaw Jaw The jaw is made up of the mandible, which comprises the lower jaw, and the maxilla, which comprises the upper jaw. The mandible articulates with the temporal bone via the temporomandibular joint (TMJ). The 4 muscles of mastication produce the movements of the TMJ to ensure the efficient chewing of food. Jaw and Temporomandibular Joint: Anatomy ( micrognathia Micrognathia Abnormally small jaw. Pierre Robin Sequence) and deformity Deformity Examination of the Upper Limbs of the zygomatic Zygomatic Either of a pair of bones that form the prominent part of the cheek and contribute to the orbit on each side of the skull. Skull: Anatomy bones, the ossicles, and the external ears (results in hearing problems). Genetic mutations Genetic Mutations Carcinogenesis resulting in too few neural crest cells Neural crest cells Gastrulation and Neurulation can cause a deficiency of neural crest cells Neural crest cells Gastrulation and Neurulation migrating to the 1st pharyngeal arch, leading to a shortage of cells required to create these structures.
• Pierre-Robin sequences: Underdevelopment of the jaw Jaw The jaw is made up of the mandible, which comprises the lower jaw, and the maxilla, which comprises the upper jaw. The mandible articulates with the temporal bone via the temporomandibular joint (TMJ). The 4 muscles of mastication produce the movements of the TMJ to ensure the efficient chewing of food. Jaw and Temporomandibular Joint: Anatomy (possibly due to positioning and/or compression Compression Blunt Chest Trauma in utero) leads to a more posterior position of the tongue Tongue The tongue, on the other hand, is a complex muscular structure that permits tasting and facilitates the process of mastication and communication. The blood supply of the tongue originates from the external carotid artery, and the innervation is through cranial nerves. Lips and Tongue: Anatomy, which in turn leads to an inability of the palate Palate The palate is the structure that forms the roof of the mouth and floor of the nasal cavity. This structure is divided into soft and hard palates. Palate: Anatomy to close (resulting in cleft palate Cleft palate Congenital fissure of the soft and/or hard palate, due to faulty fusion. Cleft Lip and Cleft Palate).
• Agnathia: rare condition in which the lower jaw Jaw The jaw is made up of the mandible, which comprises the lower jaw, and the maxilla, which comprises the upper jaw. The mandible articulates with the temporal bone via the temporomandibular joint (TMJ). The 4 muscles of mastication produce the movements of the TMJ to ensure the efficient chewing of food. Jaw and Temporomandibular Joint: Anatomy fails to form entirely.
• Goldenhar syndrome: combined malformation of the 1st and 2nd branchial arch of unknown etiology leading to abnormalities primarily affecting the eyes, ears, and spine Spine The human spine, or vertebral column, is the most important anatomical and functional axis of the human body. It consists of 7 cervical vertebrae, 12 thoracic vertebrae, and 5 lumbar vertebrae and is limited cranially by the skull and caudally by the sacrum. Vertebral Column: Anatomy. Presentation is with asymmetrical facial anomalies, including malformations of the outer ear Outer ear The outer part of the hearing system of the body. It includes the shell-like ear auricle which collects sound, and the external ear canal, the tympanic membrane, and the external ear cartilages. Ear: Anatomy (e.g., microtia, anotia), ocular tumors or dermoids, underdeveloped facial bones and muscles, and spine Spine The human spine, or vertebral column, is the most important anatomical and functional axis of the human body. It consists of 7 cervical vertebrae, 12 thoracic vertebrae, and 5 lumbar vertebrae and is limited cranially by the skull and caudally by the sacrum. Vertebral Column: Anatomy abnormalities. Other anomalies of the heart, kidneys Kidneys The kidneys are a pair of bean-shaped organs located retroperitoneally against the posterior wall of the abdomen on either side of the spine. As part of the urinary tract, the kidneys are responsible for blood filtration and excretion of water-soluble waste in the urine. Kidneys: Anatomy, lungs Lungs Lungs are the main organs of the respiratory system. Lungs are paired viscera located in the thoracic cavity and are composed of spongy tissue. The primary function of the lungs is to oxygenate blood and eliminate CO2. Lungs: Anatomy, and limbs are also possible. 

3rd and/or 4th arch conditions

• DiGeorge syndrome DiGeorge syndrome DiGeorge syndrome (DGS) is a condition caused by a microdeletion at location q11.2 of chromosome 22 (thus also called 22q11.2 syndrome). There is a defective development of the third and fourth pharyngeal pouches, leading to thymic and parathyroid hypoplasia (causing T-cell immunodeficiency and hypocalcemia, respectively). DiGeorge Syndrome: result of a 22q11.2 chromosomal microdeletion that causes abnormal formation of the 3rd and 4th pharyngeal pouches. This formation results in frequent infections Infections Invasion of the host organism by microorganisms or their toxins or by parasites that can cause pathological conditions or diseases. Chronic Granulomatous Disease from thymic hypoplasia Thymic hypoplasia DiGeorge Syndrome, hypocalcemia Hypocalcemia Hypocalcemia, a serum calcium < 8.5 mg/dL, can result from various conditions. The causes may include hypoparathyroidism, drugs, disorders leading to vitamin D deficiency, and more. Calcium levels are regulated and affected by different elements such as dietary intake, parathyroid hormone (PTH), vitamin D, pH, and albumin. Presentation can range from an asymptomatic (mild deficiency) to a life-threatening condition (acute, significant deficiency). Hypocalcemia (from abnormal parathyroid Parathyroid The parathyroid glands are 2 pairs of small endocrine glands found in close proximity to the thyroid gland. The superior parathyroid glands are lodged within the parenchyma of the upper poles of the right and left thyroid lobes; the inferior parathyroid glands are close to the inferior tips or poles of the lobes. Parathyroid Glands: Anatomy development), cleft palate Cleft palate Congenital fissure of the soft and/or hard palate, due to faulty fusion. Cleft Lip and Cleft Palate, abnormal facies (such as micrognathia Micrognathia Abnormally small jaw. Pierre Robin Sequence and low-set ears Low-set ears DiGeorge Syndrome), and cardiac defects (including, potentially, a tetralogy of Fallot Tetralogy of Fallot Tetralogy of Fallot is the most common cyanotic congenital heart disease. The disease is the confluence of 4 pathologic cardiac features: overriding aorta, ventricular septal defect, right ventricular outflow obstruction, and right ventricular hypertrophy. Tetralogy of Fallot, ventricular septal defect Ventricular Septal Defect Tetralogy of Fallot, and/or truncus arteriosus Truncus arteriosus Truncus arteriosus (TA) is a congenital heart defect characterized by the persistence of a common cardiac arterial trunk tract that fails to divide into the pulmonary artery and aorta during embryonic development. Truncus arteriosus is a rare congenital malformation with a high mortality rate within the 1st 5 weeks of life if not managed promptly. Truncus Arteriosus).
• Lateral branchial cysts Cysts Any fluid-filled closed cavity or sac that is lined by an epithelium. Cysts can be of normal, abnormal, non-neoplastic, or neoplastic tissues. Fibrocystic Change and fistulas: If the cervical sinus persists, lateral branchial cleft cysts Cysts Any fluid-filled closed cavity or sac that is lined by an epithelium. Cysts can be of normal, abnormal, non-neoplastic, or neoplastic tissues. Fibrocystic Change form. These cysts Cysts Any fluid-filled closed cavity or sac that is lined by an epithelium. Cysts can be of normal, abnormal, non-neoplastic, or neoplastic tissues. Fibrocystic Change are generally benign Benign Fibroadenoma, but they can be bothersome. Fistulas can also form between these cysts Cysts Any fluid-filled closed cavity or sac that is lined by an epithelium. Cysts can be of normal, abnormal, non-neoplastic, or neoplastic tissues. Fibrocystic Change, either with an external opening (usually at the anterior edge of the sternocleidomastoid Sternocleidomastoid Muscles of the Neck: Anatomy muscle) and/or an internal opening (leading into the supratonsillar fossa, which may result in bad breath Bad breath An offensive, foul breath odor resulting from a variety of causes such as poor oral hygiene, dental or oral infections, or the ingestion of certain foods. Oral Cancer).