Lecture 7: Developmental Genetics

• Developmental genetics


  The study of the relationships between gene regulation and cell differentiation during development
• Development


  1. Regulated growth that results from the interaction of the genome with the cytoplasm and the environment

  2. Programmed sequence of phenotypic events typically irreversible
• Determination


  A cell makes an irreversible commitment to follow a certain developmental path
• Determinants


  Cytoplasmic effector substances which cause the cells to become irreversibly committed to perform a specialized function
• Differentiation


  • Formation of different cell types, tissues, and organs through specific regulation of gene expression
  • The expression of cells' specialized role
  • Specialized cells: cells producing specialized proteins derived from luxury genes
• Gene products are not needed for survival
• Central question in developmental genetics: How one cellular genotype gives rise to many different cellular phenotypes?
• Initial cytoplasmic environment


  • Set by maternal genome
  • Triggers the switching on and off of genes
  • The gene products will occupy a specific position in the egg
  • When the cell divides, the cytoplasmic environment of each cell will be different from each other
• Formation of different cellular phenotypes


  Due to the unequal distribution of the cytoplasmic environment which triggers differential gene action
• Differential gene function is an intrinsic and fundamental aspect of cell differentiation
• Cell phenotype is a consequence of differential gene action or selective expression of its genes
• Pre-transcriptional control


  1. Selective DNA replication

  2. Condensation and decondensation of chromatin
• Transcriptional control


  1. Differential RNA synthesis

  2. Differential initiation

  3. Differential polyadenylation

  4. Differential RNA processing

  5. Selective pre-mRNA degradation
• Translational control


  1. Selective translation

  2. Stability of mRNA
• Post-translational control


  Deletion of a part of a polypeptide

  Change in the state of oxidation and reduction

  Attachment of small residue

  polymerization
• Nucleo-cytoplasmic interactions


  1. Molecular exchanges between the nucleus and the cytoplasm

  2. Control of macromolecular synthesis in the nucleus by the cytoplasm
• Gene effects on system of embryonic induction

  Organizing tissue of one organ triggers the development of another organ
• Effects of Sd (Dominant Allele)

  • Prevents normal elongation of mesonephric bud
  • Ureter which arises from the mesonephric bud must reach the kidney initial cell
  • Ureter served as organizer in the formation of the kidney
• Gene effects on endocrine system

  • Normal and mutant mice with the same rate of growth initially
  • Mutant mice stopped growing and never reached maturity
  • Absence of large cells in the anterior pituitary gland
  • No secretion of growth hormone
• Gene effects on the regulation of growth and metabolism

  • Modification of a metabolic process that is of prime importance to the whole organism
  • A metabolic process is affected affecting the characteristic of a particular region leading to change in growth of the region relative to the other parts
• Action of Cp gene

  Malformations: smaller eyes, no eyelids, misshapen head, smaller body, skeleton not ossified
• Gene effects on migrating cells

  • Genes affect differentiation and migration of cells to other regions
  • In mice, cell migration is due to W allele: melanophore migration near embryonic nerve cord, production of pigment in skin and hair, RBC migration to the blood forming tissues, migration of ancestors of germ cells to prospective genital regions
• Example of gene regulation in humans: Development of fetus and development of the nose
• 98 to 99% of DNA of chimps and humans are identical, but genes alone don't dictate the differences. It depends on molecular switches that tell genes when and where to turn on and off.