Embryonic Development: Somites, Body Folding, Heart Formation, Limb Development, and Extraembryonic Membranes

Somites

  • First segmented structures in the embryo.

  • Influence regionalization of the body and the formation of segmented structures (e.g., ribs, vertebrae, cranial & spinal nerves, muscles, etc.).

  • May influence/trigger neural crest cell migration.

Somitogenesis: Formation of Somites

  • Occurs during primitive streak regression and neurulation.

  • Paraxial mesoderm "pinches off" on each side of the neural tube and notochord, forming paired blocks of paraxial mesoderm.

  • These blocks form in columns on either side of the neural tube and notochord.

  • Waves of maturation occur such that as posterior somites form, anterior somites are already differentiating.

Somite Differentiation

  • Each somite has 3 sections:

    • Sclerotome.

    • Myotome.

    • Dermatome.

  • Each section differentiates into segmentally arranged mesodermal derivatives:

    • Dermis of the skin.

    • Muscles.

    • Axial skeletal structures (bones of the vertebral column and ribs).

Body Folding

  • The process by which the embryo becomes 3-D.

  • Involves "pinching off" the embryo from the yolk/YSE (yolk sac endoderm).

  • Occurs in the following order:

    1. Subcephalic fold (head fold).

    2. Lateral body folds.

    3. Caudal fold (tail fold).

  • As the embryo's body pinches off, the right and left sides fuse ventrally at the midline.

  • Results in:

    • A 3-D embryo "tube" fused at the midline.

    • Separation of the embryo proper from the extra-embryonic region.

    • Formation of the sides and ventral surface of the embryo.

    • Germ layers of the embryo being "tucked-in."

  • Body folding is closely linked to heart formation.

Mesoderm Differentiation

  • During neurulation, the mesoderm differentiates into:

    • Somatic mesoderm.

    • Splanchnic mesoderm.

Heart Formation

  • In the chicken, the first heartbeats occur around 33-38 hours post-fertilization.

  • Circulation is well-established by 51-56 hours.

Heart Formation Process

  1. Pre-cardiac Splanchnic Mesodermal Cells Migrate: During regression, these cells migrate and merge anterior to the head process, forming the Cardiac crescent/1o Heart field region (HFR)/Cardiogenic area.

  2. Cardiac Crescent Cells Differentiate and Proliferate

  3. Coelom Formation: Splanchnic mesoderm migrates ventrally. The coelom is the space/cavity created when the splanchnic and somatic mesoderm layers separate.

  4. Foregut Formation: Forms as splanchnic mesoderm migrates.

  5. Differentiation into Precursor Cells: Cardiac crescent cells differentiate into myocardial and endocardial precursor cells.

  6. Formation of Endocardial Tubes: Endocardial precursors form endocardial tubes.

  7. Foregut Closes into Gut Tube: Myocardial precursors are pulled ventrally.

  8. Fusion at Midline: Endocardial tubes and myocardial precursors fuse at the midline, forming a simple cardiac tube.

  • Differentiation into cardiac fibers begins.

  • All steps are made possible by body folding.

Heart Looping

  • The heart tube continues to grow and bend, "squashing" down on itself.

  • Septation occurs as the heart loops.

Limb Development

  • Another example of development, where body folding is not involved in starting formation.

Limb Fields

  • Mesenchyme from somatic mesoderm undergoes determination to become the Limb field.

    • This is the undifferentiated site of the future limb.

    • Morphogens (possibly Hox gene family products) are involved.

Limb Bud

  1. Myotome Entry: Myotome from somites enter limb fields (somites ~15-20 = wing; ~23-32 = leg).

    • These will become future muscles.

    • Morphogens: FGF-8 & FGF-10.

  2. Mesenchyme Contact: Mesenchyme + myotome contact and push the overlying surface ectoderm outward.

  3. Limb Bud Formation: The limb bud is a combination of mesenchyme + myotome + surface ectoderm.

Limb Bud Formation Details

  • Distal ectoderm induced to become Apical Ectodermal Ridge (AER)

    • Morphogen: FGF-10

    • AER = Apical ectodermal ridge

    • MES = Mesenchyme

    • PZ = Progress zone

    • ZPA = Zone of polarizing activity
      During Limb formation:

  • AER induces adjacent mesenchyme to differentiate into the Progress zone.

    • Morphogen: FGF-8

  • Progress zone cells in close contact with AER undergo rapid division.

  • The AER receives signals and differentiates, releasing morphogens back toward the limb field region (mesoderm), creating a concentration gradient effect.

Limb Development: Axes via Cell Line Interactions

Three induction interactions in the limb bud generate 3 limb axes:

  1. Proximal-distal axis: AER + Progress zone

  2. Dorsal-ventral axis: Ectoderm overlying sides of developing limb bud + Mesenchyme cells in the body of the limb bud

  3. Anterior-posterior axis: Mesenchyme cells @ the posterior margin in the base of the limb bud (Zone of polarizing activity = ZPA) + Progress zone

Proximal-Distal Axis

  • AER induces progress zone cells to proliferate.

    • Morphogens: FGFs 8 & 10

  • Progress zone cells in close contact with AER continue to proliferate.

  • Progress zone cells left behind experience morphogen concentration effects:

    • Some undergo apoptosis (morphogen concentrations = low-to-none).

    • Some just slow proliferation and come under induction influence from other inducers.

  • AER & progress zone expand distally, and cells "left behind" develop into limb regions & structures.

    • The mechanism is still uncertain.

  • Disruption/destruction/removal of AER results in truncation of the limb.

Dorsal-Ventral Axis

  • Dorsal & ventral patterns give rise to different structures.

  • AER & progress zone expand distally and cells "left behind" develop into limb regions & structures.

  • Dorsal ectoderm messages "dorsal".

    • Morphogen: WNT7a

  • Ventral ectoderm messages "ventral".

    • Morphogens: Bone morphogenic proteins (BMPs) & Engrailed1 (EN1)

Anterior-Posterior Axis

  • Prior to outgrowth, the edge of the AER contacts a small group of mesenchyme cells (from somatic mesoderm) in the posterior region of the early limb bud.

  • AER activates these cells.

    • They become the Zone of polarizing activity = ZPA.

    • Morphogen: FGF-8

  • ZPA is characterized by sonic hedgehog gene activity.

    • Morphogen: Sonic hedgehog (shh)

  • Shh concentration gradient determines digit formation.

    • Higher concentrations induce posterior structures, where concentration goes from high to low (pinky to thumb).

Extraembryonic Membranes (EEM)

  • Membranes that develop outside of the embryo.

    • Support embryonic development.

  • Develops from embryonic cells.

    • Temporarily continuous with the embryo.

    • Body folds establish a boundary between the embryo & extraembryonic regions.

Types of EEM

  • 4 EEM form during vertebrate development:

    1. Amnion.

    2. Chorion

    3. Allantois

    4. Yolk sac

  • Present to some degree in all vertebrates.

EEM Formation

  • Derived from 3 germ layers.

    • Extends out of embryo.

  • Somatopleure = Somatic mesoderm + Ectoderm.

  • Splanchnopleure = Splanchnic mesoderm + Endoderm.

EEM Summary of Origins and Functions

  • Amnion

    • Origin: Somatopleure (Somatic mesoderm + Amniotic ectoderm)

    • Function: Hydration; protection

  • Chorion

    • Origin: Somatopleure (Somatic mesoderm + Chorionic ectoderm)

    • Function: Respiration

  • Allantois

    • Origin: Splanchnopleure

    • Function: None until fusion with chorion

      • Birds (chorioallantoic membrane – CAM)

        • Origin: Splanchnopleure + Somatopleure

        • Function: Respiration + Waste management

      • Mammals

        • Chorion forms from splanchnic mesoderm + trophectoderm

        • Fuses with maternal endometrium & becomes the placenta

  • Yolk Sac

    • Origin: Splanchnopleure

    • Function: Nourishment