Human Development Week 3: Gastrulation and Embryo Formation

3rd Week of Human Development

• Objectives:
  • Understand how cell movement drives Gastrulation and the formation of a Trilaminar Embryo (3-Germ Layers)
  • Learn about the formation of the Primitive Streak and Notochord
  • Learn about the beginning of Neurulation
  • Understand the formation of the Neural Plate, Neural Tube, Neural Crest, and the Brain

Formation of the Trilaminar Embryo

• Gastrulation: conversion of a bilaminar to a trilaminar embryonic disc consisting of endoderm, mesoderm, and ectoderm
• Gastrulation begins with the formation of the primitive streak
• During Gastrulation, the embryo is individualized, and twins cannot form

Emergence of the Primitive Streak

• The primitive streak elongates medially from the thickened dorsal epiblast surface of the bilaminar embryo
• The bilaminar embryonic disc converts to a trilaminar embryonic disc as the primitive streak gives rise to the mesoderm layer
• The epiblast is now called the ectoderm layer, and the hypoblast is replaced by the endoderm layer
• Axial orientation is established, giving bilateral symmetry to the embryo

Formation of the Notochord

• The primitive streak degenerates and shortens, but adds cells to elongate the notochordal process under the epiblast
• The notochordal process induces the overlying embryonic ectoderm to form the neural plate, which gives rise to the CNS
• On Day 21, the notochordal process flanked by neural folds also begins to fold, forming a tube called the notochord

Neurulation

• The neural plate invaginates along its central axis to form a neural groove flanked by neural folds
• The neural folds fuse to form the neural tube, which delaminates from the ectoderm
• The neural tube forms the primordium of the brain vesicles, spinal cord, and retina

Neural Crest, Spinal Ganglia, and the Epidermis

• The neural fold is flanked by neural crest cells
• The neural crest cells migrate ventro-laterally and form the spinal ganglia
• The surface ectoderm becomes delaminated and fuses to form a continuous epidermis layer

Somite Formation Defines the Axial Skeleton

• Paraxial mesoderm forms between the neuroectoderm and endoderm, adjacent to the notochord
• The paraxial mesoderm differentiates, condenses, and divides into somites in a cranio-caudal sequence
• By Day 35, there are 44 somites, forming the axial skeleton

Development of Intraembryonic Coelom

• Coelomic space fuse to form a horseshoe-shaped cavity, the intraembryonic coelom
• The lateral mesoderm splits into somatic mesoderm (parietal layer) and splanchnic mesoderm (visceral layer)

Early Development of the Cardiovascular System

• Day 16: Extraembryonic mesoderm forms blood islands that fuse to form blood vessels that attach to the connecting stalk
• Day 18: Intraembryonic mesoderm forms blood islands that fuse to form blood vessels that attach to the connecting stalk and chorion
• Cranially, intraembryonic mesoderm converts to cardiogenic mesoderm, forming the early cardiovascular system and a heart primordium

Vasculogenesis and Angiogenesis

• Vasculogenesis: vascular channels form by assembly of cells called angioblasts
• Angioblasts aggregate to form clusters of blood island, which form cavities that coalesce to form primordial blood vessels
• Angiogenesis: budding, sprouting, and branching of new vessels from pre-existing endothelial vessels

Primordial Cardiovascular System

• Day 20-21: Heart and great vessels originate from the cardiogenic mesoderm
• Lacunae in the lateral mesoderm contribute to the formation of the pericardial coelom
• Paired, endothelial-lined endocardial heart tubes fuse and form a primordial heart tube

Functional Cardiovascular System

• The heart tube joins with blood vessels in the embryo, connecting the stalk, chorion, and umbilical vesicle to form a functional cardiovascular system
• The system has three branches by Day 26: the arterial system, the umbilical vein, and the vascular plexus of vitelline veins

Summary of the 3rd Week

• Initiation of gastrulation, where the embryonic disc is converted from a bilaminar to a trilaminar disc
• Formation of the primitive streak, which gives rise to the mesoderm
• Formation of the notochordal process, which induces the formation of the neural plate
• Formation of the neural tube, which gives rise to the CNS
• Development of the intraembryonic coelom, somites, and the axial skeleton### Embryo Folding and Development
• 18-24 days: Cylindrical human embryo forms with lateral body folds
• Folding occurs in two directions: longitudinal (cephalo-caudal) and lateral (transverse)
• Longitudinal folding due to rapid enlargement of cranial end of neural tube and primordial brain
• Lateral folding due to rapid enlargement of somites, leading to wrapping of amnioblast around embryo and pinching of yolk sac

Hindgut Development and Germ Layer Derivatives

• Day 28: Lateral folding fuses three germ layers in the cylinder
• Endoderm in the center forms midgut and a primordium intestine
• Foregut and hindgut are already defined earlier
• Lateral folding reduces connection between midgut and yolk sac, forming an omphaloenteric duct

Morphological Changes in Early Week-4

• Day 22-23: Major morphological changes occur in the embryo
• Day 22: Embryo is straight with ~4-10 somites
• Day 23: Medially placed neural tube has 8-10 somites, open to amniotic cavity at cranial and caudal ends

Formation of Pharyngeal Arches and Heart Development

• Day 24: First pair of pharyngeal arches (mandibular arch) emerge, forming mandible and maxilla
• Heart starts pumping blood; rostral neuropore closes

Development in the Late Week-4 Embryo

• Day 26: Three pairs of pharyngeal arches emerge at 27-somite stage
• Rostral neuropore closes, forebrain enlarges, and embryo becomes C-shaped
• Lens placode, otic pit, and nasal placode develop

Emergence of Limb Buds and Chambered Heart

• Day 27: Upper limb buds develop as small swellings on ventrolateral body
• Day 28: Fourth pair of pharyngeal arches formed; lower limb buds emerge, caudal neuropore closes, and nasal placode prominently emerges
• Primordial organ systems form; large primordial heart defines atrium and ventricular prominences