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 Hope

Phantom Menace

Attack of the Clones

Lucky to be here!

17.1

Better to be lucky than good?

occasionally livea short time

Nondisjunction

Fig 16.4

Human Syndromes• Mosaic pleiotropy• Relational pleiotropy• Genetic and Phenotypic

heterogeneity.

Teratogenesis• DDT- pesticide• Thalidomide- sedative during

pregnancies• Rubella- 1964 epidemic leading

to 20,000 blind, deaf, or both fetuses.

DDT

Thalidomide

Timing is everything

Fig. 17.5

Teratogens

• Table 17.2

Alcohol• Fetal Alcohol Syndrome

(FAS)– 1 out of 650 children

• Fetal alcohol Spectrum Disorder (FASD)– 3 times as many kids with

FASD than FAS

Retinoic Acid• Accutane: 13-cis-retinoic acid

• Hox gene expression• Pharyngeal Arches

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)

Diethylstibestrol (DES)• Gonad Development• Hoxa10 regulation• Guess who? BMP or Wnt?

17.9 then 17.11, then 17.12

Plastic bottles a source of teratogens?

• Nonylphenol

• Bisphenol A

Fig. 16.22 and 16.25

Nonylphenol• Tufts University- estrogen

responsive tumor cells• Plastic containers that held

water and serum were culprit.

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 mg per liter of BPA

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

Other teratogens• Heavy Metals• Pathogens

– Rubella- within first 6 weeks– Toxoplasma gondii

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

Cancer Stem Cell Hypothesis

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

Cancer: Epigenetic reprogramming

Cancer: Epigenetic reprogramming

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

regeneration

Anti-Angiogenesis• VEGFs• Fgfs

17.22

Embryonic Stem Cells• Embryonic stem cells• Embryonic germ cells

17.23

Induced Pluripotent stem cells• Fbx15 enhancer• OCT4, SOX2, c-MYC, and KLF4

17.25

Induced Pluripotent stem cells• Use of viral vectors• Inject fibroblasts transduced with OCT4, SOX2, KLF4, and c-

MYC.

17.26