Development

Cellular Mechanisms of Development

I. Overview of Development

  • Development involves systematic gene-directed changes throughout an organism's life cycle.

  • Divided into four subprocesses:

    • Growth (cell division)

    • Differentiation

    • Pattern formation

    • Morphogenesis

II. Cell Division

  • Post-fertilization, the diploid zygote undergoes rapid mitotic divisions:

    • In animals, this period is known as cleavage.

    • Controlled by cyclins and cyclin-dependent kinases (Cdks).

  • Cleavage results in smaller cells called blastomeres, with G1 and G2 phases shortened or eliminated.

Example of Cell Division

  • In zebrafish, blastomeres divide every several minutes, creating an embryo of thousands of cells in just under 3 hours.

  • Blastomeres are non-differentiated, potentially giving rise to any tissue.

Types of Stem Cells

  • Totipotent: Can give rise to any cell type (zygote, blastomeres).

  • Pluripotent: Can develop into all cell types (e.g., inner cell mass of blastocyst).

  • Multipotent: Can develop into a limited number of cell types (e.g., hematopoietic stem cells).

  • Unipotent: Give rise to only one tissue (e.g., spermatogonia).

Blastocyst Formation

  • Cleavage in mammals continues for 5-6 days forming the blastocyst:

    • Outer layer (trophoblast): forms the placenta.

    • Inner cell mass (embryoblast): forms the embryo; source of embryonic stem cells (ES cells).

III. Cell Differentiation

  • Human bodies contain over 210 major types of differentiated cells.

  • Cell determination commits a cell to a developmental pathway; this can be experimentally observed by relocating cells.

    • If cells adapt to their new positions, they are not determined.

Transplanting Cells

  • The standard test for cell determination involves transplanting tail cells to a head position, showing whether they maintain original fate or adopt new one based on location.

  • Differentiation is initiated through transcription factors altering gene expression patterns.

Mechanisms of Differentiation

  • Cytoplasmic Determinants: Differentiation influenced by inherited material within cells.

  • Induction: Changes in cell fate due to interactions with adjacent cells.

IV. Nuclear Reprogramming

  • Development in multicellular animals involves no changes in DNA sequences, suggesting epigenetic processes.

  • Nuclear transfer has demonstrated that determination is reversible.

  • Totipotency can be seen in early cleavage stages in mammalian embryos, allowing for identical twins' natural formation.

Cloning Advances

  • In 1984, the first successful nucleus transplant led to cloning a sheep, followed by Dolly in 1996, proving that differentiation can be reversed.

  • Challenges in cloning include low success rates and age-associated diseases due to improper genomic imprinting.

V. Pattern Formation

  • Early pattern formation establishes two axes:

    • Anterior/posterior (head-to-tail) axis.

    • Dorsal/ventral (back-to-front) axis.

  • Environmental cues inform gene activity, directing appropriate cellular fates based on location.

  • Hox geneHomeobox-containing gene that specifies the identity of a body part

  • Function as transcription factors that bind DNA using their homeobox domain

  • Ultimate targets of Hox gene function must be genes that control cell behaviors associated with organ morphogenesis

Drosophila Embryogenesis

  • Embryogenesis - fertilized egg to larva

  • Drosophila (fruit fly) undergoes metamorphosis from larval form to adult form.

  • Initial development influenced by maternal mRNAs and their gradients, affecting the anterior/posterior and dorsal/ventral formation.

  • Morphogens are signaling molecules that carry information from one group of cells to another, which helps regulate the fate of nearby cells based on their concentration

VI. Morphogenesis

  • Morphogenesis encompasses form and structure development through:

    • Cell division, shape and size, death, and migration (plants lack cell migration).

  • Environmental influences affect development:

    • Examples include germination conditions and temperature-dependent sex determination in reptiles.

Summary of Cell Migration

  • Cell migration involves adhesion and loss of adhesion mediated by cadherins and integrins interacting with extracellular matrix (ECM).

  • Apoptosis (programmed cell death) is vital for normal development, while necrosis refers to accidental cell death.