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 gene– Homeobox-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.