Lecture 19 Development and cancer “The inner life of a cell”

Four essential processes by which a multicellular organism is made

Basic anatomical scheme common to all animals exemplified here by sea urchin gastrulation Gastrulation: the transformation of a simple ball or hollow sphere of cells into a structure with a gut--an almost universal feature of animal development Ectoderm: epidermis and nervous system Endoderm: 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 interaction Some short-range Others 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 into leg structures

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

Neural crest cells migrate in specific pathways and give rise to many cell types (including skin pigment cells)

Effect of kit gene mutation Pigmentation is defective because pigment cells depend on the kit gene product to for a survival factor

Nodal is expressed on the left side Some infertile men (dynein mutation mutation--cilia and flagella beating) Left-right organs inverted

Three phases of neural development

Benign Malignant Carcinomas:epithelial cells Sarcomas: connective tissues or muscle cells Leukemias: hemopoitic cells Cancers in the nervous system Terms The common sites in the bone marrow for metastasis of the prostate cancer

Cancer incidence and mortality in the United States Year 2000 The fiive most common 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 sequence of genetic changes underlying the development of a colorectal carcinoma Steps of tumor pregression

Summary 1.The question of developmental biology is how linear genetic information encoded in DNA sequence determines the formation of 3-D structures of a multicellular organism; 2Developmental processes are highly conserved and anatomical schemes are highly similar in animals; 3Mechanisms of cell diversity, tissue morphogenesis; 4Model organisms; 5Cell migration; 6Nervous system development--circuits; 7Cancer, cancer research and biology, causes of cancer and a continuing battle…