Cell Reproduction and

Differentiation
Developmental Biology and
Cancer
Mark F. Wiser

http://www.tulane.edu/~wiser/cells/

Cell
Cycle

Initial Cleavages

several rounds of cell division without cell

growth following fertilization
16-32 cell stage (solid ball of cells) = morula

Gamete
Formation

Early Specialization

Fertilization

Initial
Cleavages

Primary Tissue
Formation
Organ
Formation

morula forms hollow ball known as

blastocyst (or blastula)
inner cell mass becomes embryo
trophoblasts are precursors to
placenta
local environment affects
subsequent specialization

Gastrulation
blastula implants gastrula
continued cell division and growth
major cell rearrangements
formation of 3 primary germ layers:
endoderm, mesoderm, ectoderm

Primary Tissue
Formation
Organ
Formation

Primary Germ Layers

primary tissues organs
process involves:
cell determination
cell differentiation
morphogenesis

Endoderm

Mesoderm

Ectoderm

o lining of digestive
system
o lining of respiratory
system
o liver
o pancreas
o glands

o muscle
o outer covering of
organs
o excretory system
o gonads
o circulatory system
o bones and cartilage
o circulatory system
o dermis

o nervous system and

brain
o epidermis and
related structures

Gamete
Formation

Cell Specialization
2 major factors influence cell fate

Fertilization

developmental history
local environment (neighboring cells)

gene expression altered

terminal differentiation
Initial
Cleavages

cessation of cell division

restricts potential to develop into
other cell types

Primary Tissue
Formation

Stem Cells
any cell with ability to divide
one progeny replaces 'stem cell'
other progeny becomes more
specialized

Organ
Formation

Stem Cells
8-cell morula

totipotent

inner cell mass

of blastocyst

pluripotent

various tissues
(bone marrow)

multipotent

embryonic

adult

Hematopoietic Stem Cells

Tumors and Cancer

Normal differentiated cells:
cell division is highly controlled
typically remain in one location
Loss of cellular controls leads to cell
replication (neoplasia)
hyperplasia benign tumor
cell structure and function altered slightly
localized mass, often encapsulated

dysplasia cancer (malignant tumor)

cell structure and function substantially altered
loss of adherence to neighboring cells
invasions of other tissues and spread
throughout body (metastasis)

Genes and Neoplasia

cell division is controlled by many different
regulatory genes
proto-oncogenes (promote cell division)
> 60 proto-oncogenes
regulatory proteins (hormones and receptors,
protein kinases, transcription factors, etc)
proto-oncogene oncogene conversion

tumor suppressor genes (inhibit cell

growth and division)
mutations or altered gene expression
contribute to neoplasia
cancer is multi-step process involving many
genes

Contributing
Factors
normal high growth rate
inherited susceptibility
chemical carcinogens
radiation
infectious agents
general health (eg, diet,
stress, etc)
immune system
some genes associated with
hereditary predisposition to
cancer function in DNA repair
breast cancer (BRCA-1, BRCA-2)

Normal epithelium

Colon Cancer
Genetic Abnormalities Detected
in Colorectal Cancer Cells
Gene
K-ras

% Tumors Class
~50

oncogene

neu

oncogene

myc

oncogene

APC

>70

tumor suppressor

DCC

>70

tumor suppressor

p53

>70

tumor suppressor

HNPCC

~15

tumor suppressor

APC, adenomatous polyposis coli; DCC, deleted in

colon carcinoma; HNPCC, hereditary nonpolyposis colorectal cancer

APC loss

Hyperproliferative
epithelium

Early adenoma
K-ras activation

Intermediate
adenoma
DCC loss

Late adenoma
p53 loss

Carcinoma
others

Metastases

Tumor Suppressor p53

mutant p53 associated with many cancers
p53 binds DNA and induces transcription
of another gene called p21
p21 binds to a complex formed between
G1 cyclin and Cdk2
G1 cyclin/Cdk2 important for transition
from G1 S phase
in presence of p21 cells remain in G1
phase (non-dividing)
in absence of p21 cells enter S phase
and divide

Summary
cells can replicate (ie, stem cells) or
differentiate into specialized cells
replication and differentiation are highly
regulated processes involving many genes
loss of controls regulating cell division can
lead to neoplastic disease