Development of Multicellular Tissues – Key Concepts

Embryonic Development

• Sequence from zygote to embryo
  • Fertilized egg → 2-cell → 4-cell → 8-cell → blastula → gastrula → embryo.
• Germ-layer formation in gastrula
  • Ectoderm, endoderm, mesoderm established.
  • Each layer is the founder tissue for specific adult structures (see final summary).

General Features of Multicellular Tissues

• Adult organism is a mosaic of tissues derived from all three germ layers.
• Continuous renewal, repair, and specialisation are hallmarks of adult tissues.

Epithelial Tissue (Epithelium)

• Definition & Origin
  • Sheet of cells separating internal milieu from external milieu (covers surfaces, lines cavities & lumens).
  • Derives from all three germ layers.
• Key characteristics
  • Unique subcellular designs & intercellular junctions (tight junctions, desmosomes, etc.).
  • Dynamic barrier: can import, expel, absorb, secrete.
  • High turnover: e.g., intestinal epithelium replaced roughly weekly.

Functional Roles

• Control permeability (selective barrier).
• Absorption / secretion.
• Physical protection & containment.

Classification

• By layers
  • Simple (single layer) → absorption/filtration where thin barrier needed.
  • Stratified (≥2 layers) → protection in high-abrasion zones (skin, mouth).
  • Pseudostratified (appears multi-layered but each cell contacts basal lamina).
• By cell shape
  • Squamous (flat, scale-like).
  • Cuboidal (≈ height = width).
  • Columnar (tall, column-shaped).
• Matrix of possibilities ⇒ simple/stratified squamous, cuboidal, columnar (see Table 4-1 reference).

Polarity

• Defined by tight junction belt.
  • Apical (free) surface → faces lumen/exterior.
  • Basolateral surface → interfaces with neighbouring cells & connective tissue.

Basement Membrane (= Basal Lamina + Reticular Lamina)

• Basal lamina: specialized ECM \approx 50-100\,\text{nm} thick.
• Reticular lamina: collagen-rich network.
• Functions
  • Structural support; tensile/compressive strength; elasticity.
  • Regulates cell access to stroma & influences division, death, differentiation, migration.
  • Guides cell migration in repair; barrier during cancer metastasis (tumour must breach BM).
  • Blood vessels do not penetrate BM—nutrients & O_2 must diffuse (\le 140\,\mu m limit).

Skin (Ectoderm-Derived)

• Largest mammalian organ; composed of epidermis (epithelium + appendages) and dermis (connective tissue).
• Associated systems
  • Extracellular matrix (fibroblast-secreted) for mechanical support.
  • Blood vessels (endothelial-lined) supply nutrients/oxygen & immune access.
  • Sensory & autonomic nerve fibres for input/output signals.

Layered Organization

• Epidermis (outer), Dermis (loose → dense CT), Hypodermis (fatty CT).
• Sensory nerves and blood vessels course within CT layers.

Interfollicular Epidermis

• Multilayered sheet mainly of keratinocytes.
  • Basal layer: mitotically active basal cells.
  • Prickle (spinous) layer: many desmosomes anchoring keratin filament bundles (visible “prickles”).
  • Granular layer: sealed to form waterproof barrier; start nuclear/organelle loss.
  • Keratinised layer: dead squames packed with keratin, eventually shed (major component of household dust).
• Turnover time \approx 30\,\text{days}.

Molecular Program

• Basal layer initiates a gene-expression cascade → sequential keratin family members + other differentiation proteins.
• Terminal differentiation coincides with permanent exit from cell cycle.

Stem-Cell Hierarchy

• Stem cells in basal layer → committed transit-amplifying cells → differentiating cells → terminally differentiated squames.

Regulation of Renewal

• Must thicken into callus under mechanical stress & rapidly repair wounds.
• Additional specialised stem-cell niches exist in appendages (hair follicles, etc.).

Epidermal Derivatives (Ectodermal Glands)

• Sweat, lacrimal (tears), salivary, and mammary glands.

Mammary Glands (Ectodermal, Modified Sweat Glands)

• Hallmark of mammals; relevance: infant nourishment, dairy industry, prevalent cancer site.
• Dynamic adult development controlled by hormonal cycles.
  • Resting gland: duct tree in fatty stroma; epithelium harbours mammary stem cells.
  • Pregnancy (estrogen + progesterone): ductal epithelial proliferation (several-hundred-fold) → branching → alveoli formation with secretory cells.
  • Lactation: milk production active.
  • Weaning: massive apoptosis eliminates secretory cells → gland regresses.

Sensory Epithelia (Specialised Ectodermal Structures)

• Common theme: epithelial organisation + neuron/neuron-like sensory transducers.
• Complex accessory structures deliver stimuli to sensory cells which convert to electrical signals → synapse with afferent neurons.

Olfactory Epithelium (Nose)

• Cell types
  • Olfactory sensory neurons (OSNs): apical immotile cilia with odorant receptors; basal axon to brain.
  • Supporting sustentacular cells.
  • Basal stem cells on BM generate new OSNs (lifetime \approx 1–2 months).
• Protective glandular secretions maintain moist surface.

Auditory Epithelium (Organ of Corti, Ear)

• Hair cells + supporting cell lattice under tectorial membrane.
• Hair cell features
  • Apical stereocilia (actin-filled, graded height) organised with frequency-specific precision.
  • Mechanical deflection opens/closes channels → membrane potential change → neurotransmitter release at basal synapse.
• Regeneration
  • Mammals: hair cells non-renewable → permanent hearing loss if destroyed.
  • Non-mammalian vertebrates: supporting cells divide & differentiate into new hair cells (potential therapeutic model).

Endoderm-Derived Organs: Airways & Gut

Lung Airways

• Formed by iterative branching culminating in \sim hundreds of millions of alveoli.
• Alveolar lining cell types
  • Type I pneumocytes: squamous, cover most surface, thin for gas exchange.
  • Type II pneumocytes: secrete pulmonary surfactant (phospholipid film) to lower surface tension, prevent alveolar collapse; begin production \approx 5 months gestation enabling preterm viability.

Respiratory Epithelium (Bronchi/Trachea)

• Pseudostratified epithelium with:
  • Goblet cells → mucus secretion (traps dust/pathogens).
  • Ciliated cells → coordinated beating to clear mucus.
  • Endocrine (small) cells → paracrine control of mucus & ciliary activity.
  • Basal stem cells for renewal.

Digestive Tract

• Functions: digestion (chemical breakdown) + absorption.
• Strategies to separate harsh digestion from delicate absorptive surfaces
  • Acid-enzyme hydrolysis confined to stomach (reaction vessel).
  • Small intestine operates at neutral pH & major absorption.
  • Protective mucus coat lines both stomach & intestine.
  • Continuous epithelial renewal (turnover \le 1 week).

Small Intestine Architecture & Renewal

• Single-layered epithelium covers villi projecting into lumen + lines crypts.
• Stem cells at crypt base divide; progeny migrate upward → differentiate into absorptive enterocytes (with dense microvilli, i.e., brush border), goblet cells, etc.
• Microvilli massively amplify apical surface area (EM shows dense striated/brush border).

Mesoderm-Derived Systems

Endothelial Cells (Blood Vessels)

• Line all vasculature; can sprout to form new vessels (angiogenesis).

Blood Cells (Hemopoietic System)

• Multipotent hemopoietic stem cell in bone marrow gives rise to all terminally differentiated blood cells.
• Blood cell types vary in lifetime; many exit vasculature to function in tissues.

Muscle

• Four principal muscle cell categories
  1. Skeletal (voluntary, multinucleate fibres, striated).
  2. Cardiac (heart; striated, branched, single nucleus/cell).
  3. Smooth (non-striated; visceral functions—gut motility, piloerection, etc.).
  4. Myoepithelial (ectodermal, within epithelia; e.g., iris dilator, glandular expulsion of saliva/sweat/milk).

Skeletal Muscle Development

• Mesodermal precursors → myoblasts.
  • Myoblasts proliferate → exit cell cycle → express muscle-specific genes → fuse into multinucleate fibres.
  • Fusion mediated by specific adhesion molecules.
  • Terminal differentiation: post-mitotic; nuclei halt DNA replication.

Growth Mechanisms

• Fibre number set prenatally; adult enlargement via:
  • Lengthening (myoblast recruitment adds nuclei).
  • Girth (hypertrophy: more myofibrils + some new nuclei).
• Satellite cells reside beneath fibre basal lamina; quiescent until injury or load stimulates proliferation/fusion for repair or growth.

Myostatin Pathway

• Myostatin (TGF-β family) secreted by skeletal muscle; inhibits myoblast proliferation & differentiation ➔ negative feedback.
• Loss-of-function mutations ⇒ dramatic muscle hypertrophy in animals & humans.
• Satellite cells also regulated by myostatin.

Three Germ Layers – Summary of Adult Derivatives

• Ectoderm
  • Skin (epidermis) + appendages (hair, glands, nails), mammary glands.
  • Sensory epithelia: olfactory neurons, auditory hair cells, retina (not detailed here).
  • Nervous system (mentioned contextually).
• Endoderm
  • Gut tube & appendages (liver, pancreas), respiratory tract (trachea, lung epithelium).
• Mesoderm
  • Muscle (skeletal, cardiac, smooth), connective tissues, blood & endothelial cells.

Ethical, Clinical & Practical Implications

• Basement membrane breach is pivotal step in cancer metastasis; understanding BM composition informs anti-metastatic therapies.
• Surfactant insufficiency in premature infants ⇒ neonatal respiratory distress; exogenous surfactant therapy life-saving.
• Permanent hair-cell loss in humans vs regenerative capacity in birds/fish stimulates research into gene therapy & stem-cell activation for hearing restoration.
• Myostatin inhibition explored for muscular dystrophy treatment and livestock production, but raises ethical concerns (doping, disproportionate growth).
• Mammary gland cyclic apoptosis a model for tissue regression; dysregulation tied to breast cancer.

Key Numbers & Equations (for quick recall)

• Basement-membrane thickness: 50\text{–}100\,\text{nm}.
• Oxygen diffusion limit through tissue: 140\,\mu m.
• Epidermal turnover time: \approx 30\,\text{days}.
• Olfactory neuron lifetime: \approx 1\text{–}2\,\text{months}.
• Surfactant production begins \approx 5\,\text{months gestation}.