1. Bad News with a side of Good news Genetic Syndromes Teratogens Endocrine disruption Cancer Anti-angiogenesis treatment Induced Pluripotent Stem Cells Regenerative Biology A New HopePhantom Menace Attack of the Clones

2. Lucky to be here! 17.1

3. Better to be lucky than good? occasionally live a short time

4. Nondisjunction Fig 16.4

5. Human Syndromes Mosaic pleiotropy Relational pleiotropy Genetic and Phenotypic heterogeneity.

6. Teratogenesis DDT- pesticide Thalidomide- sedative during pregnancies Rubella- 1964 epidemic leading to 20,000 blind, deaf, or both fetuses. DDT Thalidomide

7. Timing is everything Fig. 17.5

8. Teratogens Table 17.2

9. Alcohol Fetal Alcohol Syndrome (FAS) – 1 out of 650 children Fetal alcohol Spectrum Disorder (FASD) – 3 times as many kids with FASD than FAS

10. Retinoic Acid Accutane: 13-cis-retinoic acid Hox gene expression Pharyngeal Arches

11. Endocrine disruptors Hormonal Agonists/Antagonists Block Synthesis, elimination and transportation of hormones Prime organism to be more sensitive to hormones PCBs Diethylstibestrol (DES) Bisphenol A (BPA)

12. Diethylstibestrol (DES) Gonad Development Hoxa10 regulation Guess who? BMP or Wnt? 17.9 then 17.11, then 17.12

13. Plastic bottles a source of teratogens? Nonylphenol Bisphenol A Fig. 16.22 and 16.25

14. Nonylphenol Tufts University- estrogen responsive tumor cells Plastic containers that held water and serum were culprit.

15. Bisphenol A (BPA) Developed as a synthetic estrogen 2 Billion Pounds still produced yearly Used for: – Resin lining in most cans – Polycarbonate plastic in baby bottles, childrens toys – Dental sealant. – Brightly colored polycarbonate bottles Water in Polycarbonate bottles for week at Room Temp. – 300  g per liter of BPA

16. Bisphenol A (BPA) Low dose exposure – Meiotic defects Predispostion to breast cancer 95% of individuals tested in U.S. and Japan have measurable amounts of BPA in urine Plastics industry claims “evidence is meager” Nalgene and Wal-Mart no longer make or sell BPA containing bottles. Figure 17.13 and 17.14

17. Other teratogens Heavy Metals Pathogens – Rubella- within first 6 weeks – Toxoplasma gondii

18. Cancer: a disease of development Context dependent tumors – Cell-cell communication – Paracrine pathways Cancer Stem cell hypothesis – MITF and melanocytes Embryonic migration pathways Epigenetic reprogramming

19. Cancer Stem Cell Hypothesis

20. Cancer: a disease of development Context dependent tumors – Cell-cell communication – Paracrine pathways Cancer Stem cell hypothesis – MITF and melanocytes Embryonic migration pathways Epigenetic reprogramming

21. Cancer: Epigenetic reprogramming

23. Light at end of tunnel.. Anti-Angiogenesis Stem cells and tissue regeneration

24. Anti-Angiogenesis VEGFs Fgfs 17.22

25. Embryonic Stem Cells Embryonic stem cells Embryonic germ cells 17.23

26. Induced Pluripotent stem cells Fbx15 enhancer OCT4, SOX2, c-MYC, and KLF4 17.25

27. Induced Pluripotent stem cells Use of viral vectors Inject fibroblasts transduced with OCT4, SOX2, KLF4, and c- MYC. 17.26