Week 9 - Developmental Disorders and experiment

• methods of assessing developing foetus for altered development

  1 calculating risk using women’s age and serum levels of biochemical markers

  2 more invasive: go into uterus diagnostic test: amniocentesis and chorionic villus sampling

  2 blood test in first 10-12 weeks to detect autosomal chromosomes 13,18,21, X and Y.

  ultrasound
• do duplicated regions of chromosome always lead to altered development? Why?

  No due to feedback loops
• Why choose Ts65Dn mouse to further study?

  similar phenotype of reduction in brain volume, with hippocampus and cerebellum particularly affected like trisomy 21
• How has Ts65Dn mouse helped understand molecular basis on Down syndrome phenotypes

  Heart defects, craniofacial abnormalities like reduced mandible size; increase rise of Alzheimer’s disease due to loss of basal forebrain cholinergic neurons.
• reduced mandible Size in down syndrome thought to be caused by?

  Neural crest cells faulty migration and proliferation due to abnormal Shh signalling
• 3 major approaches to study development

  anatomical, experimental (perturb the processes and see if there is change), genetics (how genes control development)
• Modern way of doing fate mapping?


  Single cell RNA sequencing.

  collect embryos at different stages Of development.

  dissociate into single cells and barcode.

  sequence RNA in each cell

  generate map of related cells
• What experiment to do to find what cells normally do?

  Fate mapping
• Key techniques of experimental embryology

  Defect experiment: remove part of embryo and look what happens

  Transplant to another region of embryo and what happens e.g. changes cell fate
• Similarity between trisomy 21 and Ts65Dn mouse model?


  Reduction in brain volume especially hippocampus and cerebellum
• Similarities between Down syndrome babies and Ts65Dn mice?


  Delay in developmental milestones like forelimb grip and righting reflex,
• Genetic approaches to understand development

  Forward and reverse genetics
• Harmony blood test vs maternal blood test


  Harmony blood test is non invasive compared to normal pregnancy testing and checks for aneuploidy while maternal blood test idenifiy level of biomarker proteins in serum
• Which mouse chromosome is syntenic to human chromosome 21?

  16
• 3 major approaches to studying development

  Anatomical experimental and genetics