Third Week of Embryonic Development

The third week (days 15–21) is the most eventful period of early embryogenesis. It coincides with the week after the first missed menstrual period (~5 weeks after LMP). The defining event is gastrulation — the transformation of the bilaminar disc into the trilaminar germ disc.

Textbook Timeline & Events

Day 14–15 | Starting Point: Bilaminar Disc

• Epiblast — upper layer (columnar cells)
• Hypoblast — lower layer (cuboidal cells)

Day 15–16 | Gastrulation Begins: Primitive Streak

• The cranial end of the streak forms the primitive node (Hensen's node), which surrounds the primitive pit
• Key molecular drivers: FGF8 (synthesized by streak cells) downregulates E-cadherin, releasing cells from epiblast adhesion
• BRACHYURY (T-box gene) controls cell migration and mesoderm specification

Day-by-day development of the embryonic disc showing appearance of primitive streak, notochordal process, neural plate, neural groove, and notochord — The Developing Human

Day 16 | Three Germ Layers Established (Trilaminar Disc)

Derivation of all three germ layers from the epiblast through gastrulation — The Developing Human, FIG. 4.2

"The epiblast, through the process of gastrulation, is the source of all three germ layers." — Langman's Medical Embryology

Day 16–17 | Notochord Formation

1. Prenotochordal cells from the primitive node migrate cranially in the midline toward the prechordal plate
2. These cells intercalate into the hypoblast → form the notochordal plate (temporary bilaminar midline)
3. As endoderm replaces hypoblast, notochordal plate detaches → forms the definitive notochord (solid cord)

• Defines the longitudinal axis of the embryo
• Signaling center — induces formation of the axial skeleton (vertebral column)
• Induces overlying ectoderm to form the neural plate (primary neurulation)

• Oropharyngeal membrane (cranial) — tightly adherent ecto- and endoderm; future oral opening; no mesoderm here
• Cloacal membrane (caudal) — future anal/urogenital opening

Day 17–18 | Neural Induction & Allantois

Embryonic disc at 15–21 days: PS = primitive streak, PN = primitive node, N = notochord, OPM = oropharyngeal membrane, cardiogenic areas (RCA/LCA), and neural plate (NPla) — Days 15–21

• The notochord induces overlying embryonic ectoderm → thickens into the neural plate
• Allantois appears as a small diverticulum from the caudal wall of the yolk sac into the connecting stalk
  • Involved in early blood formation and development of the urinary bladder

Day 18–21 | Neurulation (Neural Tube Formation)

1. Neural plate folds longitudinally → neural groove forms in the midline
2. Lateral edges elevate → neural folds rise and converge
3. Neural folds fuse (starting at cervical level, proceeding cranially & caudally) → neural tube
4. Neural crest cells undergo epithelial-to-mesenchymal transition and migrate away bilaterally

Day 20–21 | Mesoderm Differentiation & Somitogenesis

First pair of somites appears around day 20. ~3 pairs form per day thereafter. Somite count is used to date embryos.

Throughout Week 3 | Trophoblast (Chorionic Villi) Development

Summary Flowchart (Text)

BILAMINAR DISC (Day 14)
       │
       ▼
PRIMITIVE STREAK forms at caudal epiblast (Day 15)
  └─ Primitive node (cranial) + Primitive pit
       │  (FGF8, BRACHYURY, NODAL, BMP4)
       ▼
EPIBLAST CELLS INVAGINATE through streak (Day 15–16)
  ├──→ Displace hypoblast ────────→ ENDODERM
  ├──→ Middle layer ───────────────→ MESODERM
  └──→ Remaining epiblast ─────────→ ECTODERM
                            ↓
                  TRILAMINAR DISC (Day 16)
       │
       ▼
NOTOCHORD FORMATION (Day 16–17)
  Primitive node cells → Notochordal process → Notochordal plate → Definitive Notochord
       │
       ▼
NEURAL INDUCTION (Day 17–18)
  Notochord induces ectoderm → Neural Plate
       │
       ▼
NEURULATION (Day 18–21)
  Neural plate → Neural groove → Neural folds → NEURAL TUBE
                                              └── Neural Crest cells migrate
       │
       ▼
MESODERM DIFFERENTIATION (Day 20–21)
  ├── Paraxial → SOMITES (sclerotome, myotome, dermatome)
  ├── Intermediate → Urogenital primordia
  └── Lateral plate → Intraembryonic COELOM
       │
       ▼
TROPHOBLAST: Primary → Secondary → TERTIARY VILLI (vascularized)

Clinical Correlates

• The Developing Human: Clinically Oriented Embryology (Moore & Persaud), Ch. 4 — Third Week
• Langman's Medical Embryology (Sadler), Ch. 5 — Third Week: Trilaminar Germ Disc