Lecture 19

• Development and cancer

<http://www.studiodaily.com/main/technique/tprojects/6850.html>http://www.studiodaily.com/main/technique/tprojects/6850.html

“The inner life of a cell”

Four essential processes by which a multicellular organism is made

Basic anatomical scheme common to all animalsexemplified here by sea urchin gastrulation

Gastrulation: the transformation of a simple ball or hollowsphere of cells into a structure with a gut--an almost universal feature ofanimal development

Ectoderm: epidermis and nervous systemEndoderm: gut (lung and liver)Mesoderm: muscle, connective tissues..

Conjoined (Siamese) twins

Striking results from experimental embyrology

Two ways of making sister cells different

The emergence of cell diversity

Lateral inhibition

(short-range)

Inductive interactionSome short-rangeOthers long-range

Morphogens are long-range inducers

Sonic hedgehog

The polarizing reion

The lineage tree for the cells that form the gut of C. elegans

Drosophila melanogaster A homeotic mutation

Antennapedia mutant

Antennae are converted intoleg structures

The Hox complex of insect and the Hox complexes of a mammal

Neural crest cells migrate in specific pathways and give riseto many cell types

(including skin pigment cells)

Effect of kit gene mutation

Pigmentation is defective because pigment cells depend onthe kit gene product to for a survival factor

Nodal is expressed on the left side

Some infertile men (dynein mutationmutation--cilia and flagella beating)Left-right organs inverted

Three phases of neural development

BenignMalignant

Carcinomas:epithelial cellsSarcomas: connective tissues or muscle cellsLeukemias: hemopoitic cellsCancers in the nervous system

TermsThe common sites in the bonemarrow for metastasis of the

prostate cancer

Cancer incidence and mortality in the United StatesYear 2000

The fiive mostcommon types:lung, stomach,breast, colon/rectum,uterine cervix

6 million new cases a year in the whole world

The normal and deranged control of cell production from stem cells

Viruses contribute a significant proportion of human cancers

The major signaling pathways relevant to human cancer

Suggested typical sequenceof genetic changes underlyingthe development of a colorectal carcinoma

Steps of tumor pregression

Summary

1. The question of developmental biology is how lineargenetic information encoded in DNA sequence determinesthe formation of 3-D structures of a multicellular organism;

2 Developmental processes are highly conserved and anatomicalschemes are highly similar in animals;

3 Mechanisms of cell diversity, tissue morphogenesis;4 Model organisms;5 Cell migration;6 Nervous system development--circuits;7 Cancer, cancer research and biology, causes of cancer

and a continuing battle…