W9 L3: Development and complexity

Cleavage Divisions in Early Development

• Cleavage refers to cell divisions in the early embryo without growth, producing smaller cells (blastomeres).

• During this stage, the embryo remains the same size, as divisions occur rapidly without cell enlargement.

• Totipotency: Up to the 16-cell stage, blastomeres are totipotent, meaning they can form all embryonic and extra-embryonic tissues (e.g., placenta).

• Evidence:

  • Identical twins: Formed when an early embryo splits, showing totipotency.

  • Mouse chimeras: Two 8-cell stage embryos fused, producing organisms with cells from both embryos.

  • Driesch experiments: Isolated sea urchin blastomeres separated at the 2-cell stage results in death of one cell but the surviving cell develops into a smaller but otherwise normal larvae

Totipotency vs. Pluripotency in Early Development

• Totipotency: Ability to form all embryonic and extra-embryonic tissues (e.g., placenta). Lost after the 16-cell stage.

• Pluripotency: Inner Cell Mass (ICM) cells in the blastocyst can form all embryonic tissues but not the placenta.

• Examples:

  • Embryonic Stem (ES) cells: Derived from ICM, used to create genetically modified mice.

  • Human applications: Research in regenerative medicine and genetic modification.

Cell Differentiation: Process and Types of Stem Cells

• Stages of Differentiation:

  • Specification: A reversible stage where a cell knows its fate but can change under specific conditions.

  • Commitment: Irreversible, where cells are fully specialized.

• Types of Stem Cells:

  • Pluripotent: Embryonic stem cells (e.g., ICM cells).

  • Multipotent: Can form many but not all cell types (e.g., hematopoietic stem cells for blood).

  • Unipotent: Can form only one type of cell (e.g., epidermal stem cells for skin).

  • Terminally Differentiated: Fully specialized cells (e.g., red blood cells, keratinocytes).

• Key Mechanism: Changes in gene expression regulated by transcription factors (e.g., hemoglobin in red blood cells, keratin in skin).

Programmed Cell Death in Development (Apoptosis)

• Apoptosis shapes structures by removing unnecessary cells.

• Example:

  • Digit separation in limb development: Different species use combinations of cell death and differential growth.

• Apoptosis ensures proper development and prevents malformations.

Gastrulation and Morphogenesis

• Gastrulation: Transformation of a single-layered blastula into a three-layered gastrula.

  • Layers:

    • Ectoderm: Forms skin and nervous system.

    • Mesoderm: Forms muscles, bones, and connective tissues.

    • Endoderm: Forms internal organs like the gut and lungs.

• Morphogenesis: Involves:

  • Cell movement (e.g., migration during gastrulation).

  • Changes in cell shape.

  • Altered cell adhesion (e.g., filopodia and adhesion molecules).

Organisers and Induction in Patterning (Spemann-Mangold Organizer Example)

• Induction: Cells signal to others, influencing their development.

• Spemann-Mangold Organizer:

  • Transplantation of the dorsal lip from one Xenopus gastrula to another induced a secondary body axis.

  • The organizer serves as a signaling center to direct embryo patterning.

• Zone of Polarizing Activity (ZPA):

  • Organizes anterior-posterior limb patterning by secreting Sonic Hedgehog (Shh) morphogen.

  • Transplanting ZPA to a different limb area induces symmetrical limb duplication.

Morphogens in Development

• Definition: Substances forming a gradient across tissues, producing concentration-dependent responses.

• Example: Sonic Hedgehog (Shh):

  • Secreted by ZPA, patterns the anteroposterior axis of the limb.

  • Experimental evidence: Shh-soaked beads mimic ZPA effects.

• Defects: Mutations in the Shh regulatory region cause limb patterning abnormalities (e.g., digit duplication).

Homeotic Selector Genes in Drosophila Development

• Role: Control segment identity. Mutations cause homeotic transformations (body parts in incorrect positions).

• Examples:

  • Antennapedia mutation: Antennae transformed into legs.

  • Bithorax mutation: Halteres transformed into wings, segment identity altered.

• Mechanism: Genes expressed in specific patterns along the body axis confer segment identity.

Hox Code in Vertebrates

• Function: Hox genes pattern the anteroposterior axis (e.g., head-to-tail identity in vertebrates).

• Examples:

  • Somites are patterned by Hox genes, giving rise to structures like muscles and vertebrae.

  • Hox10 knockout: Lumbar vertebrae transformed into thoracic vertebrae.

• Medical Relevance: Extra cervical ribs in humans are linked to Hox gene expression abnormalities.

Conservation of Developmental Mechanisms

• Developmental pathways are conserved across species (e.g., Shh roles in limb, brain, and midline development).

• Homologous genes (e.g., Hox, Shh) are expressed in similar patterns in different organisms.

• Example: Shh mutations result in digit duplications in both chicks and humans.

Regulatory Changes vs. Protein Coding Changes in Evolution

• Regulatory Changes: Alter when, where, and how much a gene is expressed.

  • Example: Bmp4 levels and timing influence beak shape in Darwin’s finches.

• Protein Coding Changes: Directly modify the protein.

  • Example: Mutation in insect Ubx represses leg formation in abdominal segments.

Duplication and Divergence in Evolution

• Gene Duplication: Creates genetic redundancy, allowing one copy to acquire new functions.

• Examples:

  • Hox cluster duplication enabled vertebrate body plan complexity.

  • Chordate genome duplication allowed divergence in gene function.

Modularity in Development and Evolution

• Definition: Animals are composed of modular units that can evolve independently.

• Examples:

  • Segmentation in animals provides flexibility in evolution.

  • Regulatory region modularity allows expression changes in specific tissues without widespread effects