6. Embryo, Gastrulation, and Germ Layers

Major Topics

  • Background – Preimplantation Development

  • Foundational Information – Gastrulation

  • Broader Research/Clinical Context – Modeling Gastrulation

  • Bigger Picture – From Differentiation to Body Patterning

Early Human Development

  • Fertilization Process:

    • Involves sperm and egg, produced by meiosis.

    • Results in the formation of the zygote (1 cell), which undergoes multiple rapid rounds of mitosis, a process called cleavage.

Stages of Early Development:
  • Day 0: Fertilization

  • Day 1: First cleavage and formation of the 2-cell stage.

  • Day 2: Development into the 4-cell stage.

  • Day 3-4: Forms an 8-cell uncompact morula, then compacted morula by Day 4.

  • Day 5: Development into early blastocyst with trophectoderm and an inner cell mass.

  • Days 6-8: Implantation occurs with formation of epiblast and hypoblast layers.

Gastrulation Process

  • Definition: Phase in embryonic development where embryonic morphology is restructured.

  • Formation of three embryonic germ layers:

    • Ectoderm: Epidermis, CNS, sensory organs.

    • Mesoderm: Muscles, connective tissues, circulatory system.

    • Endoderm: Digestive tract, lungs, liver.

Key Concepts:
  • Gastrulation begins: At approximately Day 6-8 post-fertilization in humans.

  • Cells of the inner cell mass (ICM) delaminate to form:

    • Upper layer: Epiblast (forms main embryonic tissues)

    • Lower layer: Hypoblast (forms extra-embryonic tissues like yolk sac)

  • Formation of Primitive Streak: Marks the beginning of gastrulation, indicating the axis for symmetry and further differentiation.

Directional Events in Gastrulation

  • Left-Right Asymmetry:

    • Achieved by nodal flow generated by monocilia on the node.

    • Essential for proper organ positioning and arrangement.

Disrupted Gastrulation

  • Abnormalities such as Sirenomelia can occur, resulting from insufficient mesoderm formation, leading to:

    • Fusion of lower limbs, vertebral abnormalities, and more.

    • Associated with maternal diabetes or mutations in key genes (e.g., Brachyury).

Research and Model Organisms

  • Study of Gastrulation in Humans & Chickens:

    • Chickens are particularly useful due to their large embryos and manipulation possibilities.

    • Sea urchins also serve as important model organisms because of ease in visualization during gastrulation.

Summary of Gastrulation

  • Human Gastrulation Timeline: Occurs from Days 8-15 post-fertilization.

  • Critical Steps:

    • Development of the primitive streak leading to establishment of axial gradients and germ layer differentiation.

    • Formation and movement through the primitive groove allow for the generation of ectoderm, mesoderm, and endoderm.

Key References

  • Carlson, B. M. (2009). Human Embryology and Developmental Biology, 4th Edition.

  • Gilbert, S. F. (2010). Developmental Biology, 9th Edition.

  • Wolpert, L. (2002). Principles of Development, 2nd Edition.

Important Considerations

  • The study of gastrulation reveals not only patterns of embryonic development but also highlights the genetic and environmental factors influencing developmental biology.

  • The beauty of gastrulation and the methodologies to explore it are enhanced by advancing technologies such as adaptive light-sheet microscopy which captures cellular movements and tissue morphogenesis at an unprecedented resolution.


  • Fertilization Process: Fertilization generally takes place in the fallopian tubes in humans.

  • Basic Cellular Structure for Movement: Cilia on the cells of the fallopian tube help move the embryo toward the uterus.

  • Stage of Implantation: A human embryo implants into the uterine wall during the early blastocyst stage, specifically around Day 5 post-fertilization.

  • Major Structural Change for Interaction: The blastocyst must undergo a process called hatching, where the outer layer (trophectoderm


  • Fertilization Process: Fertilization generally takes place in the fallopian tubes in humans.

  • Basic Cellular Structure for Movement: Cilia on the cells of the fallopian tube help move the embryo toward the uterus.

  • Stage of Implantation: A human embryo implants into the uterine wall during the early blastocyst stage, specifically around Day 5 post-fertilization.

  • Major Structural Change for Interaction: The blastocyst must undergo a process called hatching, where the outer layer (trophectoderm


  • Which part of the embryo undergoes gastrulation?
    The inner cell mass (ICM) of the embryo undergoes gastrulation, specifically the epiblast cells that will form the main embryonic tissues.

  • What is the first sign of gastrulation?
    The formation of the primitive streak marks the beginning of gastrulation, indicating the axis for symmetry and further differentiation.

  • What are the 3 germ layers? Order them from top to bottom.

    1. Ectoderm (top layer): Forms the epidermis, CNS, and sensory organs.

    2. Mesoderm (middle layer): Forms muscles, connective tissues, and the circulatory system.

    3. Endoderm (bottom layer): Forms the digestive tract, lungs, and liver.

  • What are 2 types of cell movement required during gastrulation?

    1. Epiboly: The expansion and thinning of the epiblast layer as cells spread to cover the surface.

    2. Invagination: The inward folding of a region to form a pocket, contributing to the formation of the germ layers.

  • Why are the sea urchin and the chick useful models of gastrulation?
    Sea urchins are useful for visualization during gastrulation due to their transparency and ease of manipulation. Chick embryos are also advantageous because of their large size, which allows for easy experimental alteration and observation of


  • What basic cellular structure is required to drive nodal flow?
    Cilia on the cells of the embryonic node are required to generate nodal flow.

  • In what direction is nodal flow, normally?
    Nodal flow typically moves from left to right across the embryonic axis.

  • What is the outcome if nodal flow is not functional?
    If nodal flow is not functional, it can lead to abnormal left-right asymmetry, resulting in developmental disorders and improper organ placement.

  • Name 2 factors involved in driving left-right asymmetry.

    1. Nodal: A signaling molecule crucial for establishing left-right asymmetry.

    2. Lefty: Another signaling molecule that plays a role in the left-sided signaling pathway.

  • List 4 anatomical aspects that are positioned/patterned through nodal flow and left/right patterning.

    1. Heart positioning

    2. Lateralization of the lungs

    3. Spleen placement

    4. Stomach orientation