Germ Layers and Major Derivatives

Gastrulation establishes three definitive germ layers: ectoderm, mesoderm, and endoderm. Every tissue and organ in the body derives from them.

Knowing the germ layer origin of an adult tissue is one of the most powerful organising tools in embryology. It predicts the structures a congenital anomaly is likely to affect together. It also predicts the embryonic mechanisms that could plausibly have gone wrong to produce it.

Ectoderm is the outermost germ layer. It gives rise to two broad categories of tissue: the entire nervous system, and the surface covering of the body.

The nervous system derives from ectoderm via neurulation. This includes:

• The entire central nervous system, brain and spinal cord, formed from the neural tube itself
• A substantial part of the peripheral nervous system, formed from the neural crest, a specialised, highly migratory ectodermal cell population that delaminates from the neural folds

Neural crest derivatives include the sensory neurons of the dorsal root ganglia and cranial sensory ganglia, the postganglionic neurons and supporting cells of the autonomic nervous system, Schwann cells, and the adrenal medulla.

The surface ectoderm is the portion of ectoderm that does not form neural tissue. It gives rise to the epidermis of the skin and all of its appendages: hair follicles, nails, and cutaneous glands (sweat glands, sebaceous glands, and mammary glands).

Surface ectoderm also forms:

• The lens of the eye and the epithelium of the cornea
• The epithelial lining of the external auditory meatus and the outer layer of the tympanic membrane
• The anterior pituitary gland, formed from an ectodermal outpocketing called Rathke's pouch
• The enamel of the teeth
• The epithelial lining of the oral cavity, nasal cavity, and anal canal below the pectinate line

Neural crest cells are ectodermal in origin, but their derivatives extend well beyond conventional nervous tissue. They form:

• The bones and connective tissue of the face and much of the skull
• The dental pulp
• Melanocytes throughout the skin
• The septum of the outflow tract of the heart
• The smooth muscle and connective tissue of the walls of the large arteries arising from the aortic arches
• The parafollicular, calcitonin-secreting, cells of the thyroid gland

Mesoderm is the middle germ layer. It has a broad distribution and many structures depend on it, so it gives rise to the greatest diversity of adult tissue types of any germ layer.

Paraxial mesoderm is arranged in segmented blocks called somites flanking the notochord and neural tube. It gives rise to the axial skeleton (vertebrae and ribs), the skeletal musculature of the trunk and limbs, and the dermis of the back.

Intermediate mesoderm gives rise to the urogenital system: the kidneys, ureters, and the gonads. It also forms the genital duct systems, the mesonephric and paramesonephric ducts, from which the internal male and female reproductive tracts respectively derive.

Lateral plate mesoderm splits into two layers, splanchnic and somatic, enclosing the intraembryonic coelom between them.

• Splanchnic mesoderm surrounds the developing gut tube. It gives rise to the connective tissue, smooth muscle, and vasculature of the gastrointestinal and respiratory tracts, and contributes the visceral serous membrane covering the organs.
• Somatic mesoderm, together with overlying ectoderm, forms the body wall. It gives rise to the dermis of the anterior and lateral trunk and the parietal serous membrane lining the body cavities.

Mesoderm also gives rise to:

• The entire cardiovascular system: the heart, blood vessels, and blood cells themselves, formed from specialised mesodermal cell clusters called blood islands
• The spleen, formed from mesenchymal condensation within the dorsal mesentery
• The connective tissue and cartilage of most of the body excluding the head and neck region
• The muscular layer of the gut tube, and smooth muscle
• The cortex of the adrenal gland, in contrast to the ectodermally derived medulla

Endoderm is the innermost germ layer. It is folded into the interior of the embryo during cephalocaudal and lateral folding to form the epithelial lining of the primitive gut tube and its derivatives.

The primitive gut tube is divided into foregut, midgut, and hindgut. Endoderm forms the epithelial lining of the entire gastrointestinal tract from the mouth to the upper anal canal above the pectinate line. It also forms the epithelial component of every gland that buds from this tube during development.

Foregut endoderm gives rise to the epithelial lining and glandular tissue of the oesophagus, stomach, and proximal duodenum. Via outgrowths from the foregut, it gives rise to the liver and biliary system and the pancreas.

It also gives rise to the epithelial lining of the lower respiratory tract: trachea, bronchi, and lungs. These form as a ventral outpouching of the foregut, the respiratory diverticulum.

Endoderm also forms the epithelial component of the thyroid gland, the parathyroid glands, and the thymus. All derive from the pharyngeal pouches, outpocketings of the pharyngeal portion of the foregut.

The epithelial lining of the middle ear cavity and auditory tube derives from the first pharyngeal pouch specifically.

Endoderm gives rise to the epithelial lining of the urinary bladder and most of the urethra. These derive from the urogenital sinus, itself formed by partitioning of the cloaca, the terminal expanded portion of the hindgut. Endoderm also contributes the epithelial lining of the vagina.

Germ layer origin explains why certain congenital anomalies cluster together anatomically even though they appear in seemingly unrelated organ systems.

The urogenital system (kidneys, gonads, and genital ducts) derives from intermediate mesoderm. The vertebral column and cardiac septa both derive from mesodermal structures developing in close temporal and spatial proximity. Disruptions affecting one mesodermal derivative during the relevant critical period therefore frequently co-occur with anomalies in another. This underlies several recognised clinical associations between renal, vertebral, and cardiac anomalies.

Germ layer origin also explains the tissue composition of specific tumour types. A teratoma is a tumour arising from a pluripotent germ cell. It characteristically contains tissue derived from all three germ layers within the same mass:

• Hair and skin (ectodermal)
• Cartilage and muscle (mesodermal)
• Gut or respiratory epithelium (endodermal)

This directly reflects the pluripotent cell of origin's capacity to differentiate along any of the three germ layer lineages.