Embryology Site

http://www.cellbio.emory.edu/courses/medi510/

Karl Saxe contacts:room: Whitehead Research Building Room 405Fphone: 404-727-6248e-mail: karl@cellbio.emory.edu

John Rolston contacts:room: Whitehead Research Building Room 405Le-mail: jrolston@neuro.gatech.edu

BlackBoard site: http://classes.emory.edu/webapps/login

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 correlations 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-embryonic 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

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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. Saxe 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 mechanisms in oncogenesis Mon 8/7 9:00 FINAL EXAM (2 hr)

1. Cell growth and division - refers to the increase in size (growth) and number (division) of cells in the organ or tissue.

2. Cell Differentiation - refers to the mechanism by which different sorts of cells arise. Deals with the way genes are activated or repressed and how the activity of the genes is subsequently maintained.

3. Morphogenesis - refers to the cell and tissue movements that give the developing organ its specific three dimensional shape. It depends on the dynamics of the the cytoskeleton and other mechanical properties of the cells.

4. Regional specification (aka pattern formation) - the process of generating pattern in a previously similar population of cells. Involves the intercellular mechanisms collectively called induction.

Major Hallmarks of Development

The Genetic Basis of Development

A human being contains >200 different cell types all of which are derived from a single fertilized egg.

So the Big Questions are:

1. During the course of development do cells lose genetic information, i.e. totipotency?

2. Totipotent or not, what are the genetic processes responsible for the phenotypic variation of somatic cells, i.e. cellular differentiation?(a) How does a cell know where it is and should be?(b) How does a cell know what it should be (or be doing)?(c) How does it know when it should be doing something at all?(d) How are the “right” genes turned on and the “wrong” genes turned off?(e) How general are the mechanisms of control of cellular differentiation?

DAY 7DAY 8

DAY 9

DAYS 10-12

DAYS 12-13

DAYS 14-15

Gastrulation begins with the delamination of the definitive endoderm

EARLY WEEK 3

Gastrulation produces the first dramatic changes in form

Different cells move through the primitive streak at different times, positions and rates leading to the formation of different cells and tissues HOW?

Differential gene expression and its consequences

Levels of Gene Regulation:

1. Transcriptional:

a. DNA Binding proteins/transcription factors b. Methylation of DNA at CpG sequences/miRNAs

c. Altered chromatin structure/miRNAs 2. Post-Transcriptional:

a. differential splicing b. differential RNA stability/miRNAs & siRNAs 3. Translational:

a. masking mRNA (e.g. maternal messages) b. change in concentration of translation initiation factor c. RNA binding proteins

4. Post-Translational:

a. protein modification examples: glycosylation phosphorylation isoprenylation proteolytic cleavage

Promoters & Enhancers can dictate where a gene is expressed

A single transcription factor can interact with different partners to affect expression of different genes

Some Major Transcription Factor Families and Subfamilies

The homeodomains is only one part of complex proteins