MEDI 510 (IBS 518)

1. MEDI 510 (IBS 518) July 24 - August 7, 2006 Human Embryology: Development and Disease Charles Saxe, Ph.D., Course Director Text: Moore, K.W., The Developing Human, W.B. Saunders Co., 7th ed., 2003 Place: Week 1 : lectures and clinical cor relations will be in Whitehead Auditorium Week 2: lectures and clinical correlations will be in the WHSCAB Auditorium Exams: all exams will be in the WHSCAB Auditorium Day Date Time Event Speaker Title Mon 7/24 9:00a Lect 1 Dr. Saxe Basic mechanisms of differentiation 11:00 Lect 2 Dr. Saxe Morphogenesis and cell interactions 11:45p Corr K. Torrente Intro to information retrieval at Emory Tues 7/25 9:00 Lect 3 Dr. Saxe Principles of teratogenesis 11:00 Lect 4 Dr. Saxe Gametogenesis and fertilization 1:00p Clin Corr Dr. Mitchell Advances in in vitro fertilization Wed 7/26 9:00 Clin Corr Ms Kinlaw Neonatal ethics 10:30 Lect 5 Dr. Saxe Extra - embryoni c membranes; placenta 1:00p Lect 6 Dr. Saxe Urogenital system I. Gonads Thur 7/27 9:00 Lect 7 Dr. Saxe Urogenital system II. Renal development 11:00 Clin Corr Dr. Smith Anomalies of the urinary tracts Fri 7/28 9:00 Lect 8 Dr. Moberg Ectoderm - neurulation; CNS formation 10:45 Clin Corr Dr. Sladky Congenital Neural defects ================================================================================== Mon 7/31 9:00 MIDTERM (1 hr) Tues 8/1 9:00 Lect 9 Dr. Saxe Cardiovasc I. Heart,CV system Septation 10:30 Lect 10 Dr. Saxe Cardiovasc II. Congenital heart defects 11:30 Clin Corr Dr.Sutherland Common congenital heart defects Wed 8/2 9:00 Lect 11 Dr. Sax e Mesoderm I. limb and muscle; mitotic mechanisms 10:30 Lect 12 Dr. Saxe Mesoderm II. Limb and skeletal formation 1:00p Clin Corr Dr. Weil Congenital limb anomalies Thur 8/3 9:00 Lect 13 Dr. Saxe Endoderm I. Respiratory system 10:30 Lect 14 Dr. Saxe Endoderm II. Gut, Liver, Pancreas 1:00p Clin Corr Drs Nasr and Anomalies of the gut Williams Fri 8/4 9:00 Lect 15 Dr. Saxe Cancer: Developmental mecha nisms in oncogenesis Mon 8/7 9:00 FINAL EXAM (2 hr)

3. Congenital anomalies can present in many ways Liu Junjie, a 3-month-old baby boy who was born with three arms, is shown in a Shanghai, China, hospital. On Monday, June 5, surgeons removed the lower left arm.

6. Piebaldism results from mutation in the kit gene

9. Thalidomide is a textbook example of a teratogen

10. Before the advent of the thalidomide tragedy, it had often been assumed that the maternal biosystems of hepatic detoxification and metabolism, together with the placental barrier, acted as a shield and were a natural protection for the embryo from any maternal exposure to drugs. As subsequent findings of congenital malformations in humans exposed to various agents became apparent, e.g., Rubella (Gregg, 1941), nitrogen mustard (Haskin, 1948), androgenic hormones (Wilkins and Baltimore, 1960), the folic acid antagonist, aminopterin (Thiersch and Philips, 1950; Warkany et al., 1960), and methylmercury (Tackeuchi et al., 1959; Eto and Takeuchi, 1978; Takeuchi et al., 1996), so did the realization of the susceptibility of the developing embryo. However, it was not until after the "thalidomide disaster," when a direct relationship was identified between increased incidence of phocomelia (failure of the development of limbs) and exposure to thalidomide during pregnancy (McBride, 1961; Lenz, 1961), that regulatory agencies began to recognize the importance of including teratogenicity testing (Goldenthal, 1966 [FDA, 1966]; WHO, 1967; HWC, 1975). In fact, prior to 1960, testing of chemicals during the reproductive cycle included the only recommended protocol at the time and that was the 6-wk toxicity test in male and female rodents (Anderson, 1993). Assessments and evaluation were performed over two pregnancies and fetal survival noted (Anderson, 1993).

11. GENOMIC (GERMLINE) IMPRINTING • Refers to the differential expression of genetic material, at either the chromosomal or allelic level, depending on whether the genetic material has come from the male or female. May result from errors in DNA methylation. • Examples of Evidence of Genomic Imprinting: • 1. expression in transgenic mice • 2. pronuclear transplants in mice • - human homologs of these: • a. hydatidiform moles – placental tissue with no apparent embryo • - only paternal-derived material present • b. teratomas – embryonic tissue with no apparent placenta • - only maternal-derived material present • 3. Chromosome deficiencies in mice and humans • - human example: deletion of part of 15q11-13 • a. if maternal material is deleted = Angelman Syndrome • b. if paternal material is deleted = Prader-Willi Syndrome • 4. Specific gene expression in mice and humans (> 30 known genes that show imprinting in humans) • - human examples: early onset myotonic dystrophy and early onset Huntington’s chorea • Beckwith-Wiedemann syndrome (probably IGF-2 gene)

12. Angelman Syndrome - ataxia (uncoordinated muscle movements) - seizures/ severe mental retardation - hyperactive & small and thin - lack of speech - “puppet face” children/inappropriate laughter

13. Prader-Willi Syndrome - mild mental retardation and motor development - severe hypotonia (loss of muscle tone) - short stature and obesity