Gastrulation & Segmentation in Vertebrate Embryos: Part A

Understand how the anterior-posterior body axis is formed.
Understand the basic processes of gastrulation and the formation of three germ layers.
Understand how somites are formed sequentially and periodically during embryogenesis.

Vertebrates are classified as bilaterians, possessing bilateral symmetry with a distinct anterior-posterior (AP) body axis.
They exhibit a serial repetition of structures along the body axis, known as segmentation.

During gastrulation, cells from the epiblast migrate into the primitive streak.
- Migration involves an epithelial to mesenchymal transition; cells move beneath the epiblast.
- Resulting cell populations give rise to the endoderm and mesoderm.

Zygote → Blastula → Gastrula
Structure:
- Ectoderm responsible for skin, nervous system.
- Mesoderm gives rise to muscles, bones, and blood cells.
- Endoderm forms the digestive and respiratory systems (e.g., lung cells, thyroid tissue).

Structural orientation:
- Anterior, posterior
- Transverse, coronal/frontal, lateral plate mesoderm
- Paraxial mesoderm, intermediate mesoderm, endoderm, notochord

Segmental organization is prominent in various animal groups, including vertebrates, enabling diverse body parts to form from similar structures during development.

Somites originate from unsegmented mesoderm:
- Balls of epithelial tissue that bud from paraxial mesoderm.
- Formation initiates at the anterior end and progresses toward the posterior.
- Somite formation occurs at a consistent rate (e.g., 1 somite every 90 minutes in chickens; 1 every 2 hours in mice).

The axial skeleton (excluding the skull) derives from somites, highlighting their role in segmental development.
- Somites form sequentially and in pairs through a clock and wavefront model.

FGFs control cell motility and elongation during embryo development.
- An increase in FGF concentration in posterior regions inhibits segmentation.
- Excess FGF prevents normal somite formation, crucial for maintaining the embryo's elongation gradient.

FGF8 is expressed in a gradient within the presomitic mesoderm (PSM).
- The decay of FGF mRNA produces a gradient that regulates axial elongation and segmentation timing.

The segmentation clock is facilitated by the cyclic expression of Hes1 in the PSM:
- Hes1 functions as a transcription factor and homologous to the hairy gene in Drosophila, aiding in somite segmentation.

The segmentation process leads to a repeated arrangement of tissues along the embryonic axis, orchestrated by the clock and wavefront model.

Classification of vertebrae into anatomical domains (cervical, thoracic, etc.).
Understanding that cells in segments have retained positional identities along the anterior-posterior axis.
The role of Hox genes in controlling segment identity along the axis.

Each segment possesses a defined identity dictating the type of tissues formed,
- Example: Cervical vertebrae, which lack rib attachments.

Segment identity is established before the actual segmentation.
- Transplanting pre-segmented mesoderm to a different position retains its identity (e.g., thoracic mesoderm forms thoracic vertebrae).

Hox genes encode for transcription factors influencing morphological development; they are evolutionarily conserved across species.
The comparison between Drosophila and mice shows strong functional conservation across the animal kingdom.

The anterior-to-posterior expression of Hox genes correlates with the vertebral formula during embryonic development.
Variation in vertebral identity due to Hox gene expression helps explain differences observed in related species:
- Example: Mammals typically have 7 cervical vertebrae, while birds and some reptiles have more.

Studies of knockout mice show that mutations in Hox genes lead to identity changes in vertebrae:
- Mice lacking Hox10 genes display transformations from lumbar to thoracic vertebrae.
- Mice with defective Hox11 genes show transitions from sacral to lumbar vertebrae.

There’s a relationship between gastrulation and axial patterning:
- Hox gene expression occurs in the primitive streak, with anterior Hox genes influencing early-stage mesoderm cells.
Cells expressing posterior Hox genes leave the streak later, aiding the formation of subsequent somites.

The establishment of the anterior-posterior axis is segmented in vertebrates, developed through the sequential addition of somites.
This segment identity is predetermined during gastrulation originating from cells exiting the primitive streak.

“It is not birth, marriage, or death, but gastrulation, which is truly the most important time in your life.” — Lewis Wolpert (1929–2021)

Dubrulle, J., McGrew, M. J., & Pourquié, O. (2001). FGF Signaling Controls Somite Boundary Position and Regulates Segmentation Clock Control of Spatiotemporal Hox Gene Activation. Cell, 106, 219-232.
Benazeraf, B., Francois, P., Baker, R. E., Denans, N., Little, C. D. & Pourquié, O. (2010). A random cell motility gradient downstream of FGF controls elongation of an amniote embryo. Nature, 466, 248-252.
Iimura, T. & Pourquié, O. (2006). Collinear activation of Hoxb genes during gastrulation is linked to mesoderm cell ingression. Nature, 442, 568-571.