Genes in Development

• Every cell nucleus contains the complete genome established in the fertilized egg. In molecular terms, the DNAs of all differentiated cells are identical.
• The unused genes in differentiated cells are not destroyed or mutated, and they retain the potential for being expressed.
• Only a small percentage of the genome is expressed in each cell, and a portion of the RNA synthesized in the cell is specific for that cell type.
• Differentiation - the process by which an individual cell acquires a specialized function
• Differentiation requires a change in the pattern of gene expression in a cell.
• Osteogenesis : Bone

  Chondrogenesis : Cartilage

  Myogenesis : Muscle

  Marrow Stroma : Marrow

  Tendogenesis/Ligamentogenesis : Tendon/Ligament

  Adipogenesis : Adipose Tissue
• Mesengenic Process

  Proliferation > Commitment > Lineage Progression > Differentiation > Maturation
• Differential Gene Expression


  Each cell in the body has exactly the same genome but different sets of genes are active (turned ON) in different types of cells.
• Gene Amplification - selective increase in the number of copies of a gene coding for a specific protein without a proportional increase in other genes.
• Amplification results to increased protein activity and uncontrollable cell growth.
• Gene Amplification - multiple replication of a section of the genome
• Polytene chromosomes - in the salivary gland cells of the fruitfly Drosophila
• Lampbrush chromosomes - occur in the oocytes (germ cells in the ovary) of amphibians and in some insects
• Lampbrush chromosomes - extremely large synapsed homologous chromosomes which can be seen in the diplotene stage of meiotic prophase I
• Polytene chromosomes - formed by the fusion of centromeres of all the 8 chromosomes found in the cell
• chromomeres - arms with dark bands
• chromonemata - arms with light bands
• parts of polytene chromosomes:

  1. arms
  2. chromocenter
• short arm - fused chromosome 4
• chromonemata - result from repeated replication of DNA, without separation into daughter chromosomes
• polytene chromosomes are produced by endoreplication
• Balbiani rings - particular regions of the chromosomes would occasionally form different reversible puffs (chromosome puffs) which are associated with differential gene activation.
• Polytene chromosomes increases production of mRNA for Glue Protein
• parts of lampbrush chromosome:

  1. axis
  2. loops
• axis consist of:

  • chromomeres (nucleosomes)
  • interchromomere regions
• loops are consist of transcriptionally active DNA
• Reticulocytes synthesize hemoglobin.
• Morphogenesis is the process by which differentiated cells are organized into a hierarchy of tissues, organs, and organ systems.
• Nuclear Pore Complex - control traffic in and out of the nucleus and manage transfer of proteins
• 2 mechanisms of NPC

  1. Passive Diffusion - for small molecules to move freely
  2. Selective - aka energy-dependent transport; for macromolecules
• Import Cycle

  1. Nuclear localization signal (NLS) on protein binds to importin
  2. Protein-importin complex enters nucleus and binds to Ran-GTP
  3. Protein dissociates
  4. Importin and Ran-GTP complex moves to the cytoplasm
  5. GTP is hydrolyzed to GDP and importin dissociates.
• Export Cycle

  1. Proteins in the nucleus are marked with Nuclear Export Signals/NLS, binding to Exportins.
  2. Cargo proteins bind with Exportins and RAN-GTP for transport.
  3. Cargo proteins detach in the cytoplasm, while Exportin-RAN-GTP complex moves out.
  4. The complex relocates to the cytoplasm.
  5. GTP hydrolysis triggers Exportin dissociation.
• small nuclear RNAs are initially exported from the nucleus to the cytoplasm, where they associate with proteins to form small nuclear RNA-protein complexes. The assembled snRNPs are then transported back into the nucleus.

  
• Reception - A cell detects a signaling molecule from the outside of the cell. A signal is detected when the chemical signal (ligand) binds to a receptor protein on the surface of the cell or inside the cell.
• Transduction - binding of signaling molecule alters the receptor and initiates a signal transduction pathway
• Response - the signal triggers a specific cellular response.
• Cell Signaling

  
• Intracellular Receptors and Direct Gene Activation

  1. The steroid hormone diffuses through the plasma membrane and binds an intracellular receptor.
  2. The receptor-hormone complex enters the nucleus.
  3. The receptor-hormone complex binds a specific DNA region.
  4. Binding initiates transcription of gene to mRNA.
  5. The mRNA directs protein synthesis.
• The Spemann Mangold experiment consisted of a series of graftings in which some cells were removed from the dorsal side of a frog embryo and then transplanted to the other side of a second embryo. The transplanted dorsal cells caused the embryo to develop a second set of complete body structures. (gastrulation)
• Mutations in key hormone-synthesis genes cause endocrine disorders.