Embryo - Midterms

• Chromatin


  A complex of DNA and proteins (histones)
• Nucleosome


  The basic unit of chromatin structure
• Components of a nucleosome


  • An octamer of histone proteins
  • 140 base pairs of DNA
  • Joined together by linker DNA
• Heterochromatin


  Chromatin that is inactive and coiled, cannot be transcribed
• Euchromatin


  Chromatin that is uncoiled
• Gene parts


  • Exons (contain DNA sequences that can be translated into proteins)
  • Introns (found in between exons, cannot be translated into proteins)
  • Promoter region (where RNA polymerase binds for transcription start)
  • TATA box (usually contains the sequence TATA)
  • 5' (transcription initiation site)
  • Translation initiation site
  • Translation termination codon
  • 3' Poly A addition site (untranslated, assists with mRNA stabilization and exit from nucleus)
• Gene transcription


  1. DNA is transcribed from 5' to 3' end

  2. Transcription factors (protein complex) bind to TATA box in promoter region to allow RNA polymerase binding

  3. Transcription factors have DNA-binding domain and transactivating domain

  4. Transcription factors activate gene expression by unwinding DNA nucleosome complex
• Enhancers


  Regulatory parts of DNA that activate utilization of promoters to control efficiency and rate of transcription
• Silencers


  Enhancers that inhibit transcription
• DNA methylation of cytosine bases in promoter regions represses gene transcription
• Genomic imprinting - only a gene inherited from the father or the mother is expressed
• Nuclear RNA (nRNA)


  Initial transcript of a gene, longer than mRNA, contains introns that are removed (spliced out)
• Alternative splicing


  Forms different proteins from the same gene
• Spliceosomes


  Complexes that recognize specific splice sites
• Induction


  One group of cells or tissues causes another set of cells or tissues to change their fate; how organs form
• Inducer


  Produces signal that initiates induction
• Responder


  Responds to the induction signal
• Competence


  Capacity to respond to a signal, requires activation of responding tissue by a competence factor
• Epithelial-mesenchymal interactions


  Needed for differentiation to continue
• Crosstalk


  Communication between tissues or cells, needed for differentiation
• Paracrine interactions


  Involve diffusible proteins
• Paracrine factors


  Growth and differentiation factors
• Juxtacrine interactions


  No diffusible proteins involved
• Paracrine signaling


  1. Paracrine factors act by signal transduction pathways

  2. Receptor has ligand-binding region, transmembrane domain, and cytoplasmic domain

  3. Ligand binding activates receptor's cytoplasmic domain, often through phosphorylation

  4. Phosphorylation of proteins activates transcription factors to regulate gene expression
• Paracrine signaling factor families


  • Fibroblast Growth Factor (FGF)
  • WNT
  • Hedgehog
  • Transforming Growth Factor-Beta (TGF-Beta)
• Fibroblast Growth Factors (FGFs)


  Stimulate growth of fibroblasts, important for angiogenesis, axon growth, and mesoderm differentiation, activate FGFRs
• Hedgehog proteins


  Code for a pattern of bristles on the leg that look like a hedgehog, Sonic hedgehog involved in many developmental events
• WNT proteins


  Involved in regulating limb patterning, midbrain development, and somite and urogenital differentiation
• TGF-Beta superfamily


  Important for forming extracellular matrix, epithelial branching, and bone formation, regulates cell division, cell death, and cell migration
• Other paracrine signaling molecules

  • Neurotransmitters (serotonin, GABA, epinephrine, norepinephrine)
  • Act as ligands and bind to receptors
• Sonic Hedgehog (SHH)


  A master morphogen/gene involved in the development of many tissues and organs
• Sonic Hedgehog signaling


  1. SHH protein binds to Patched receptor, this stops Patched from inhibiting Smoothened

  2. Activated Smoothened upregulates GLI transcription factors to control target gene expression

  3. SHH is cleaved and cholesterol is added to its N-terminal domain, Dispatched releases SHH from the plasma membrane
• Planar cell polarity (PCP)


  Regulates the process of convergent extension, the reorganization of cells and cell sheets in the plane of a tissue
• Convergent extension


  A process in which a tissue becomes longer and narrower, like the elongation of the neural plate to form the neural groove
• Notch pathway


  Notch receptors bind to DSL ligands, binding results in cleavage of Notch protein which then goes into the nucleus and binds to a DNA-binding protein to regulate transcription
• Processes and structures Notch signaling is involved in


  • Cell proliferation
  • Apoptosis
  • Epithelial to mesenchymal transitions
  • Neuronal differentiation
  • Blood vessel formation
  • Somite segmentation
  • Pancreatic beta-cell development
  • B- and T-cell differentiation
  • Development of inner ear hair cells
  • Septation of heart's outflow tract
• Alagille syndrome is caused by a NOTCH mutation and involves cardiac outflow tract defects and other abnormalities
• Primordial germ cells (PGCs)


  Where gametes come from, formed in the epiblast during the second week of development and migrate to the gonads
• Gametogenesis


  The process of preparing germ cells for fertilization, includes meiosis and cytodifferentiation
• Teratomas


  Tumors that often contain a variety of tissues, may arise from pluripotent PGCs or epiblast cells