Embryonic Germ Layers & Epithelial-Mesodermal Derivatives

Embryonic Development Overview

• Fertilisation → sequential cleavage: 2-cell → 4-cell → 8-cell → morula → blastula → gastrula → embryo.
• Gastrulation = first major cell-fate decision; produces 3 primary germ layers.
  • Endoderm (inner infolding)
  • Mesoderm (intermediate layer)
  • Ectoderm (outer layer)
• Potency changes
  • Zygote/totipotent blastomeres → pluripotent inner‐cell‐mass → multipotent germ-layer cells.

Epithelium – General Features

• Only tissue derived from all three germ layers.
• Literal meaning: “laid-on covering.”
• Functions
  • Physical barrier; containment of body fluids.
  • Selective permeability: absorption & secretion.
  • Dynamic (high turnover) e.g. intestinal lining replaced \approx 7\text{ days}.
• Universal architecture
  • Sheet of closely apposed, polarised cells.
  • Interface between internal milieu & external environment (skin; mucosae; serosae; gland ducts).

Classification of Epithelia

• By LAYERS
  • Simple – one cell thick; optimised for diffusion/absorption (e.g. lung alveoli, kidney tubule).
  • Stratified – \ge 2 layers; protection in high-abrasion sites (skin, oral mucosa).
  • Pseudostratified – nuclei at different heights; looks multilayered but is simple (trachea).
• By SHAPE (height vs width)
  • Squamous – flat, scale-like.
  • Cuboidal – cube-like; \text{height}\approx\text{width}.
  • Columnar – tall, column-shaped.
• Combinatorial examples (histology images)
  • Simple squamous, cuboidal, columnar.
  • Stratified squamous, cuboidal, columnar (+ transitional/pseudostratified if encountered).

Epithelial Polarity & Junctional Complexes

• Regions
  • Apical (free) – faces lumen/exterior; may bear cilia, microvilli, stereocilia.
  • Lateral – cell–cell contacts.
  • Basal – rests on basement membrane.
• Tight junction (zonula occludens) delineates apical vs basolateral domains; forms diffusion barrier.

Basement Membrane (BM)

• Composite ECM platform under every epithelium.
  • Basal lamina: specialised matrix (laminin, type-IV collagen) \approx 50!–!100\,\text{nm}.
  • Reticular lamina: collagen-rich layer anchoring to underlying connective tissue.
• Functions
  • Mechanical support, elasticity, resistance to compression.
  • Filter regulating passage to interstitium/capillaries.
  • Influences cell polarity, proliferation, differentiation, survival.
  • Barrier to tumour invasion; carcinoma must breach BM for metastasis.

Germ-Layer–Specific Tissue Outcomes (Key Examples)

• Ectoderm
  • Epidermis + appendages (hair, nails, sweat, sebaceous, mammary glands).
  • Nervous system, sensory epithelia (olfactory, auditory, retinal).
• Mesoderm
  • Muscle (skeletal, cardiac, smooth, myoepithelial), connective tissue, endothelium, blood.
• Endoderm
  • Gut epithelium, liver, pancreas, lungs/airways, thyroid etc.

Ectodermal Derivative I – Epidermis & Hair Follicle

• Skin = largest mammalian organ; multi-layered interfollicular epidermis between hair follicles.
• Epidermal strata (basal → surface)
  1. Basal layer – cuboidal stem cells (unipotent); only mitotic layer.
  2. Prickle (spinous) – keratin filament “spines.”
  3. Granular – keratohyalin granules; tight junctions create water-proof barrier.
  4. Cornified squames – dead, enucleated, keratin-packed; shed as dust.
• Turnover time \approx 30\text{ days}.
• Hair follicle bulge houses multipotent epidermal stem cells → hair shaft, sebaceous gland, interfollicular keratinocytes.
• Regulation: mechanical load → callus; wound healing; hormonal control.

Ectodermal Derivative II – Mammary Gland

• Modified sweat gland; development continues in adult.
  • Pregnancy hormones (oestrogen, progesterone) → massive duct/alveolar proliferation (×10^2).
  • Lactation: alveoli filled with milk; myoepithelial contraction for ejection.
  • Weaning: apoptosis & tissue remodelling.
• Illustrates adult morphogenesis plus cycles of cell-cycle entry & programmed cell death.

Ectodermal Derivative III – Sensory Epithelia

Olfactory Epithelium

• Cell types
  • Olfactory sensory neurons (OSNs) – apical cilia with odorant receptors; axons traverse BM to olfactory bulb.
  • Sustentacular (supporting) cells – mechanical & metabolic support.
  • Basal (stem) cells – replenish OSNs every \approx 1!–!2\text{ months}.
  • Bowman's gland cells – secrete serous fluid maintaining moist surface.

Auditory (Cochlear) Epithelium – Organ of Corti

• Auditory hair cells (inner & outer) – apical stereocilia graded by height; mechanotransduction (sound → ionic flux → receptor potential).
• Supporting cells hold hair cells in precise array.
• Basilar & tectorial membranes convert pressure waves → shear forces.
• No resident stem cells; hair-cell loss = permanent deafness (contrast with regenerative birds/amphibians).

Endodermal Derivative I – Respiratory Epithelium

Distal Airway (Alveolus)

• Cell types
  • Type I pneumocytes – squamous; >95\% surface; gas exchange.
  • Type II pneumocytes – cuboidal; secrete pulmonary surfactant (phospholipid film) preventing surface-tension collapse.
• Surfactant synthesis starts \approx 5 fetal months → viability threshold.

Proximal (Conducting) Airways

• Pseudostratified ciliated columnar epithelium.
  • Goblet cells → mucus.
  • Ciliated cells → coordinated beating; mucociliary escalator (debris → pharynx → swallowed).
  • Basal stem cells → renew epithelium.
  • Neuro-endocrine cells modulate mucus/ciliary rate.

Endodermal Derivative II – Gastrointestinal Tract

• Stomach: acid hydrolysis (low pH) + pepsin; mucous coat protects epithelium.
• Small intestine: neutral pH; primary absorption.
  • Villi & microvilli ↑ surface area (brush border).
  • Crypts of Lieberkühn house stem cells (bottom); non-dividing differentiated enterocytes migrate up villus and shed within <7\text{ days}.
• Design balances harsh digestion with constant epithelial renewal.

Mesodermal Derivative I – Endothelium & Angiogenesis

• Simple squamous epithelium lining all blood & lymph vessels.
• Functions: barrier, coagulation control, leukocyte trafficking, vasoregulation, angiogenesis.
• New sprouts form when endothelial cells break BM, migrate, proliferate, lumenise.

Mesodermal Derivative II – Blood (Haematopoiesis)

• All blood lineages derive from multipotent haemopoietic stem cell (HSC) in bone marrow.
  • Continuous production because mature blood cells have finite lifespans.

Mesodermal Derivative III – Muscle Tissue

• Four contractile cell types
  1. Skeletal (striated, multinucleate, voluntary).
  2. Cardiac (striated, branched, intercalated discs, involuntary).
  3. Smooth (non-striated, spindle-shaped, involuntary in viscera, vessels, piloerection).
  4. Myoepithelial (ectoderm-derived; contract gland acini/ducts, iris).

Skeletal-Muscle Ontogeny

• Mesodermal precursors → myoblasts (mononuclear).
• Myoblasts exit cell cycle, express muscle-specific genes, fuse → syncytial multinucleated myofibre.
• Striations = ordered actin–myosin sarcomeres.

Growth & Repair

• Post-natal fibre number fixed; growth via:
  • Hypertrophy (↑ diameter): addition of myofibrils, nuclear accretion.
  • Lengthening: incorporation of new myoblasts at fibre ends.
• Satellite cells (quiescent stem cells under basal lamina) → activated after injury or load → proliferate → differentiate → fuse with fibres or form new fibres.

Myostatin – Negative Regulator

• Secreted TGF-β-family protein from muscle.
• Autocrine/paracrine inhibition of myoblast proliferation & differentiation.
• Loss-of-function mutation → “double-muscling” (e.g. Belgian Blue cattle, myostatin-knockout mice); potential target for cachexia therapy/sports doping.

Integrated Themes & Clinical Correlates

• Basement-membrane breach crucial step in carcinoma metastasis.
• Stem-cell niches provide protection (hair-bulge, intestinal crypt, epidermal rete ridges).
• High-turnover epithelia (gut, olfactory, skin) vulnerable to chemotherapy/radiation.
• Surfactant deficiency → neonatal respiratory distress syndrome; treated with exogenous surfactant & glucocorticoids to accelerate type II cell maturation.
• Ciliary dyskinesia ⇒ impaired mucociliary clearance → recurrent respiratory infections.
• Myostatin pathway manipulation under investigation for muscular dystrophy.