ANA 206: Systemic Embryology I

Diaphragm, Cardiovascular, Respiratory, and

Gastrointestinal Systems
This section covers the embryonic development of several major organ systems.

Diaphragm Development
The diaphragm forms from the fusion of several embryonic structures:
Septum transversum: A mesenchymal partition that grows dorsally from the ventral body
wall.
Dorsal mesentery of the esophagus: This structure contributes to the formation of the
pleuroperitoneal membranes.
Pleuroperitoneal membranes: These membranes extend from the body wall to close the
pleuroperitoneal canals.
Muscular ingrowth from the body wall: This contributes the muscular component of the
diaphragm.

Cardiovascular System Development

Heart Tube Formation: Early in development, the mesoderm forms a bilaminar structure that
folds to create a primitive heart tube. This tube has distinct regions that will develop into the
four chambers of the adult heart.
Septation: The heart undergoes complex septation to divide the single chamber into right and
left atria and ventricles, and to separate the pulmonary and systemic circulations. Key septa
include the atrial septum, ventricular septum, and aorticopulmonary septum.
Great Vessel Development: The aorta and pulmonary artery develop from the truncus
arteriosus, and their separation is crucial for establishing the two circulatory loops.
Associated Anomalies:
Atrial Septal Defects (ASDs): Incomplete closure of the atrial septum can lead to shunting
of oxygenated blood from the left atrium to the right atrium.
Ventricular Septal Defects (VSDs): Incomplete closure of the ventricular septum results in
blood shunting between the ventricles.
Tetralogy of Fallot: A complex congenital heart defect characterized by four anomalies:
pulmonary stenosis, ventricular septal defect, overriding aorta, and right ventricular
hypertrophy.

Respiratory System Development

Lung Bud Formation: The respiratory system originates from an outpouching of the foregut
called the respiratory diverticulum (lung bud).
Branching Morphogenesis: The lung bud undergoes extensive branching to form the
bronchial tree, airways, and alveoli. This process is regulated by signaling pathways involving
growth factors and transcription factors.
Pleural Cavities: The pleural cavities, which surround the lungs, develop from the coelomic
 cavity.
Associated Anomalies:
Tracheoesophageal Fistulas: Abnormal connections between the trachea and esophagus,
often associated with esophageal atresia.
Pulmonary Agenesis/Hypoplasia: Underdevelopment or complete absence of lung tissue.

Gastrointestinal System Development

Foregut, Midgut, and Hindgut:
The primitive gut tube is divided into three main regions, each giving rise to specific organs.
Foregut: Pharynx, esophagus, stomach, upper duodenum, liver, gallbladder, pancreas.
Midgut: Lower duodenum, jejunum, ileum, cecum, appendix, ascending colon, proximal
transverse colon.
Hindgut: Distal transverse colon, descending colon, sigmoid colon, rectum, upper anal
canal.

Rotation: The midgut undergoes significant rotation to position the intestines correctly within
the abdominal cavity.
Associated Anomalies:
Esophageal Atresia: The esophagus ends in a blind pouch, preventing food from reaching
the stomach.
Intestinal Atresia/Stenosis: Narrowing or complete blockage of the intestine.
Meckel's Diverticulum: A remnant of the vitelline duct, which connects the midgut to the
yolk sac.

Urogenital, Musculoskeletal, and Integumentary

Systems, and Limbs
This section details the development of the urinary, reproductive, skeletal, muscular, and
integumentary systems, as well as the formation of the limbs.

Urogenital System Development

Urinary System:
Kidneys: Develop from the intermediate mesoderm through a series of three successive
primordia: pronephros, mesonephros, and metanephros. The metanephros forms the
permanent kidneys.
Ureters, Renal Pelvis, Calyces, and Collecting Ducts: Develop from the ureteric bud, an
outgrowth of the mesonephric duct.
Bladder and Urethra: Develop from the urogenital sinus, an endodermal derivative.

Reproductive System:
Gonads (Testes/Ovaries): Develop from the gonadal ridges, which arise from the
intermediate mesoderm.
Genital Ducts (Wolffian/Mullerian): The presence or absence of Y chromosome and
subsequent hormone production determines the development of either the Wolffian
 (male) or Mullerian (female) duct system.
External Genitalia: Develop from the cloaca and genital tubercle.

Associated Anomalies:
Renal Agenesis: Absence of one or both kidneys.
Hypospadias: An opening of the urethra on the ventral side of the penis.
Cryptorchidism: Undescended testes.

Musculoskeletal System Development

Skeletal System:
Axial Skeleton: Derived from the somites (vertebrae and ribs) and neural crest cells (skull).
Appendicular Skeleton: Derived from the limb buds, which are formed by mesenchyme
originating from the somites and lateral plate mesoderm.

Muscular System:
Skeletal Muscles: Primarily derived from the somites (epaxial and hypaxial muscle
components).
Smooth and Cardiac Muscles: Derived from the splanchnic mesoderm.

Associated Anomalies:
Scoliosis: Abnormal curvature of the spine.
Limb Defects (e.g., Amelia, Meromelia): Absence or incomplete development of limbs.
Clubfoot (Talipes Equinovarus): Foot deformity where the sole is turned inward and
downward.

Integumentary System Development

Epidermis: Derived from the ectoderm.
Dermis: Derived from the mesoderm (dermatome of somites and lateral plate mesoderm).
Appendages: Hair, nails, sweat glands, and sebaceous glands develop from epidermal
invaginations into the dermis.
Associated Anomalies:
Ichthyosis: A group of genetic skin disorders characterized by dry, scaly skin.
Albinism: Deficiency or absence of pigment in the skin, hair, and eyes.

Limb Development
Limb Buds: Appear as outgrowths of the body wall around the 4th week of gestation.
Apical Ectodermal Ridge (AER): A thickening of ectoderm at the distal tip of the limb bud,
crucial for proximal-distal outgrowth.
Zone of Polarizing Activity (ZPA): A signaling center in the posterior mesoderm of the limb
bud, responsible for anterior-posterior patterning.
Digit Formation: The distal part of the limb bud flattens to form the hand or foot plate.
Apoptosis of the tissue between the digits leads to their separation.
Associated Anomalies:
Syndactyly: Fusion of fingers or toes.
 Polydactyly: Presence of extra fingers or toes.

Molecular Regulation and Associated

Developmental Anomalies
This section focuses on the molecular mechanisms controlling embryonic development and
common anomalies.

Molecular Regulation
Signaling Pathways: A variety of signaling pathways, including Wnt, Shh (Sonic hedgehog),
FGF (Fibroblast Growth Factor), and BMP (Bone Morphogenetic Protein) pathways, play
critical roles in cell-to-cell communication, pattern formation, and differentiation during
embryogenesis.
Transcription Factors: Genes encoding transcription factors are activated or repressed by
these signaling pathways, leading to the expression of specific proteins that dictate cell fate
and tissue development.
Hox Genes: A family of genes that specify regional identity along the anterior-posterior axis of
the developing embryo, including the vertebral column and nervous system.

Associated Developmental Anomalies

General Principles:
Many developmental anomalies arise from disruptions in these molecular signaling pathways
or gene expression. This can lead to:
Abnormal cell proliferation or apoptosis.
Incorrect cell migration or differentiation.
Failure of tissue fusion or separation.
Mispatterning of structures.

Examples:
Holoprosencephaly: A severe disorder caused by failure of the forebrain to divide properly,
often linked to Shh pathway defects.
Congenital Heart Defects: Can result from disruptions in signaling pathways that regulate
heart tube formation and septation.
Limb Malformations: Often associated with problems in AER or ZPA signaling, or
alterations in Hox gene expression.

Development of the Pharyngeal Apparatus and

Derivatives, Head and Neck, Face, Eye, Ear, Tongue,
and Teeth, Thyroid and Parathyroid Glands, Sinuses
This section covers the complex development of structures in the head and neck region.
Pharyngeal Apparatus (Branchial Apparatus)
Components:
The pharyngeal apparatus consists of pharyngeal arches, pharyngeal pouches, pharyngeal
grooves, and pharyngeal membranes.
Pharyngeal Arches: Bilateral mesenchymal proliferations on the lateral aspects of the
pharynx. Each arch contains a core of mesenchyme (derived from neural crest cells and
paraxial mesoderm), an artery, a nerve, and a cartilaginous rod.
Pharyngeal Pouches: Endodermal evaginations from the pharyngeal wall, located between
the arches.
Pharyngeal Grooves: Ectodermal depressions on the outer surface of the pharynx,
between the arches.
Pharyngeal Membranes: Thin membranes formed by the apposition of ectoderm and
endoderm at the bottom of the pharyngeal grooves.

Derivatives:
Each component gives rise to specific structures:
1st Arch: Mandible, malleus, incus, muscles of mastication, trigeminal nerve.
2nd Arch: Stapes, styloid process, lesser horn of hyoid bone, muscles of facial expression,
facial nerve.
3rd Arch: Greater horn of hyoid bone, stylopharyngeus muscle, glossopharyngeal nerve.
4th and 6th Arches: Laryngeal cartilages, intrinsic laryngeal muscles, vagus nerve.
1st Pouch: Tympanic cavity, mastoid air cells, auditory tube.
2nd Pouch: Palatine tonsils.
3rd Pouch: Inferior parathyroid glands, thymus.
4th Pouch: Superior parathyroid glands, ultimobranchial bodies (contribute to C-cells of
thyroid).
1st Groove: External auditory meatus.

Head and Neck Development

Face: Develops from the frontonasal prominence, maxillary prominences, and mandibular
prominences. Fusion of these structures forms the face.
Nose: Develops from the medial and lateral nasal prominences.
Palate: Develops from the primary palate (intermaxillary segment) and secondary palates
(outgrowths from the maxillary prominences).
Tongue: Develops from swellings in the floor of the pharynx, primarily from the 1st, 2nd, 3rd,
and 4th branchial arches.
Teeth: Develop from ectodermal invaginations (dental lamina) into the underlying
mesenchyme.

Eye and Ear Development

Eye: Develops from the optic vesicles (outgrowths of the diencephalon), which form the
retina, and the surface ectoderm, which forms the lens and cornea.
Ear:
External Ear: Derived from the first pharyngeal groove and surrounding mesenchymal
proliferations.
Middle Ear: Derived from the first pharyngeal pouch and ossicles from the first two
branchial arches.
 Inner Ear: Develops from the otic placode, which invaginates to form the otic vesicle.

Thyroid and Parathyroid Glands, Sinuses

Thyroid Gland: Develops from an endodermal downgrowth in the floor of the pharynx. It
descends to its final position in the neck.
Parathyroid Glands: Develop from the endoderm of the third and fourth pharyngeal pouches.
Sinuses: Develop from evaginations of the nasal cavities into the surrounding bones.

Molecular Regulation and Associated Developmental

Anomalies
Key Signaling Centers: The development of head and neck structures is orchestrated by
complex interactions between signaling centers, including the isthmic organizer and various
pharyngeal arch signaling centers.
Neural Crest Cells: Play a critical role in the formation of many craniofacial bones, cartilage,
and connective tissues.
Associated Anomalies:
Cleft Lip and Palate: Due to incomplete fusion of facial prominences or palatine shelves.
Branchial Cysts and Fistulas: Remnants of pharyngeal pouch or groove development.
Thyroglossal Duct Cysts: Remnants of the thyroglossal duct.
Microphthalmia/Anophthalmia: Small or absent eyes, often due to abnormal optic vesicle
development.
Congenital Deafness: Can result from anomalies in any part of the ear.

Development of the Endocrine System, Central and

Peripheral Nervous Systems, Pituitary and Pineal
Glands
This section covers the development of the nervous system and key endocrine glands.

Endocrine System Development

Pituitary Gland:
Develops from two sources:
Anterior Pituitary (Adenohypophysis): Develops from Rathke's pouch, an ectodermal
outgrowth of the oral ectoderm.
Posterior Pituitary (Neurohypophysis): Develops from an outgrowth of the diencephalon
(infundibulum).

Pineal Gland: Develops from an outpouching of the epithalamus (diencephalon).

Thyroid and Parathyroid Glands: (Covered in the previous section).
Adrenal Glands:
Adrenal Cortex: Derived from mesodermal cells.
Adrenal Medulla: Derived from neural crest cells.
Central Nervous System (CNS) Development
Neural Plate, Tube, and Crest:
Neural Plate: Ectodermal thickening that forms early in development.
Neural Tube: Formed by the folding and closure of the neural plate. It is the precursor to
the brain and spinal cord.
Neural Crest: Cells that arise from the dorsal aspect of the neural tube and migrate to
various locations to form peripheral nervous system components, meninges, and other
structures.

Brain Development: The anterior part of the neural tube differentiates into three primary
vesicles: prosencephalon (forebrain), mesencephalon (midbrain), and rhombencephalon
(hindbrain). These further subdivide into the major brain structures.
Spinal Cord Development: The caudal part of the neural tube forms the spinal cord.
Ventricles and Cerebrospinal Fluid (CSF): The central cavity of the neural tube forms the
ventricular system, which contains CSF.

Peripheral Nervous System (PNS) Development

Cranial and Spinal Nerves: Develop from neural crest cells and motor neuroblasts originating
from the neural tube.
Autonomic Nervous System: Develops from neural crest cells and neuroblasts from the
spinal cord.

Molecular Regulations, Developmental Anomalies, and

Clinical Syndromes
Patterning Genes: Genes like Hox genes and Pax genes are crucial for specifying regional
identity and development of the CNS.
Growth Factors and Neurotrophic Factors: Essential for neuronal survival, growth, and
differentiation.
Associated Anomalies and Syndromes:
Anencephaly: Absence of a major portion of the brain, scalp, and skull, due to failure of
the neural tube to close properly at the cranial end.
Spina Bifida: A defect in the closure of the vertebral column, often associated with neural
tube defects.
Hydrocephalus: Accumulation of excess CSF within the ventricles of the brain, often due
to blockage of CSF flow.
Congenital Hypopituitarism: Insufficient production of pituitary hormones, often due to
developmental defects of the pituitary gland.
CHARGE Syndrome: A complex genetic disorder with multiple congenital anomalies,
including issues with the eyes, ears, heart, trachea, esophagus, and genitals, often linked
to genetic factors affecting development.