chapetr 16 - development, stem cells and cancer

What do proper embryonic development require

requires specific gene products be expressed in a given set of cells at a specific time due to differential activity of transcription factors and regulatory molecules

3 processes required in embryonic development

1. Cell division through mitosis

2. Cell differentiation, were cells become specialized in strcuture and function through alteration in cell behaviour

3. Morphogenetic, development of organisims form requiring alterations in cell behaviour

Why do cell differentiation and morphogensis express different genes

Controlled by factors present in the egg prior to fertilization

Cytoplasmic determinants in the egg

• egg contains proteins, mRNA and cellular structures produced by the organism

• They’re not uniformly distributed and provide the initial stimulus for differential gene expression in the embryo due to unequal cellular contents

How early embryo change due to induction

• As early embryos develop, the cells get influenced by its environment

• Cells at the bottom of the early embryo are releasing molecules that signal (induce) nearby cells to change their gene expression through interactions of cell surface molecules and growth factors

• Ex. Morula → blastula

Determination

• point at which an embryonic cell is committed to becoming a specific cell types after going through so many changes

• Once this occurs, it will continue to differentiate (develop) into that cell types even its environment or location changes

Differentiation

Process where a cell attains (reaches) its determine fate

What does cellular differentiation require

The expression of tissue specific protein and sequential expressio of specific genes, which leads to observable alterations in cellular structure

Most common way of regulating differentiation

Transcription

Cellular differentiation in muscle cells

• Signals from surrounding cells result in induction into a myoblast

• MyoD is expressed and the myoD transcription factor is produced and goes on to interact with other muscles

myoD in muscle cells

• activates its own transcription, producing positive feedback

• It also activates muscle specific transcription factor genes by binding to control elements in enhancers

• Muscle specific transcription factors go on to activate other genes responsible for producing specific muscle proteins and proteins that prevent cell division

Apoptosis

• form of programmed cell death either for development or getting rid of dead/malfunctioned cells

• Occurs to cells in bth embryonic and mature organisms

What occurs in apoptosis

Internal components of the cell are relegated for destruction

• cells can become multi-lobbed or experience blebbing which triggers cells to be engulfed by phagocytic cells

Development of apoptosis

• mechanism of how apoptosis worked was done by studying the soil worm

• Showed that apoptosis happens at very specific, predictable time points and is triggered by specific signal transduction pathways

• Important for the normal development of the nervous system and morphogensis of hands/feet/paws

Pattern formation

Process by which tissues and organs are spatially organized into their characteristic places

Positional information And its importance

Refers to the molecular cues that control pattern formation

• it informs the cell the location of its body axes and their neighbouring cells

• Determines how the cell and its descendants will respond to molecular signals

Homeotic genes

Regulatory genes that control pattern formation in the late embryo, larva and adult.

Axis establishment

Established due to cytoplasmic determinants in the egg

Maternal (egg donor) effect genes

Genes which when mutated in the egg donor result in mutant phenotypes in the offspring, regardless off the offsprings own genotypes

2 body axis

Anterior - posterior (front and back)

Dorsal - ventral (top and bottom)

Bicoid

Involved in anterior posterior axis formation

Morphology gradient hypothesis

Gradients of substances called morphogens determines the axes and other features

What breakthroughs were found when working With bicoid

• established the role of a specific protein in pattern formation

• Increased our understanding of the critical role played by the egg donor and their genes in early embryogenesis

• Established the role of gradients of morphogens in polarity ad position

Embryonic genes

Determine the formation of segments and their characteristic structures

What occurs to egg donor mRNA as embryogenesis proceeds

The egg donor mRNA that established anterior posture and dorsal ventral axes are no longer needs and get targeted for destruction

Cloning process

Process where new organisim is formed with the exact same genetic composition to the parent

2 types of cloning

1. Organismal - cloning whole organisim

2. Cell cloning - asexual reproduction of unicellular organisms

Why clone?

• began to determine if a single differentiated cell could be used to produce a whole new organism

• Helped to prove that differentiated cells did not lose genes but rather had different gene expression than other

Animal cloning

• Used nuclear transplantation where they removed nucleus on an egg cell and replaced it with the nucleus of a differentiated cell

• Only worked when the differentiated nucleus came from a cell early on in embryology not when it was fully differentiated

What does it mean for a cell to be enucleated

Taking its nucleus out the cell

What did Plant cloning prove

the cloning of a carrot helped prove that

• differentiation did not cause irreversible change to the cells DNA

• Totipotent cells are able to dedifferentiate and give rise to all forms of specialized cells and are able to multiply on their own

Reproductive cloning

• nucleus from a donor mammary cell was combined with an enucleated egg cells

• The blastocysts from early stage of emobryogenesis are then implanted into a surrogate uterus to continue its development

When and who was the first reproductive mammal

Dolly the sheep in 1997

Why was dollys reproduction more successful than a frog

1. Mammary cells develop in a shorter period of time

2. Blastocyst has more support through the surrogacy

Epigenetics in cloning and why clones are more easily defected

• as a cell progresses down its differentiation pathway, the DNA is altered through methylation and acetylation of histone proteins

• Reversing these epigenetic changes is difficult

Stem cells

• Unspecialized cells which have the potential to reproduce indefinitely and differentiate into specialized cells of one or more types (pluripotent)

• culturing stem cells outside the body can be used in medicine

Animal and adult stem cells

• animal embryonic stem cells can be harvested from early embryos in the blastula stage (blastocysts)

• Adult organisms also have stem cells which replace non reproducing cells

Induced pluripotent stem cells

Cells that have been deprogrammed from differentiated cells back to embryonic stem cells

• aids in regenerative medicine and studies of various diseases

What regulatory genes and products help tightly regulate the cell cycle

• growth factors and receptors

• Intracellular signalling molecules

• Anchorage dependence factors

Mutation in cell cycle

• may lead to cancer

• May be spontaneous

• Due to exposure to mutagens (chemical, physical or biological)

Oncogenes

• form of gene which when expressed leads to development of cancer (mutated proto oncogene)

• Found in viral genomes in humans and animals cells

• Leads to deregulation of cell cycle activity

Proto oncogenes

• normal cellular versions of oncogenes

• expression of these gens leads to regular cell cycle activity

Tumour suppressor genes

• product of these genes inhibit cell divsion, prevent uncontrolled cel growth and decrease their activity contributes to cancer

• Functions include DNA repair, cell adhesion, and cell signalling pathways that inhibit cell cycle density dependent inhibition where contact with other cells prevent cell division

Cancer development

• development of cancer requires multiple mutations

• Generally needs at least one active oncogene and loss of activity of several tumor suppressor genes

• This explains the increase of cancer rate with age

Cancer inheritance

• familial association has been found with certain types of cancer

• Individuals with inherited mutations require less new mutations to form cancer

• Baseline level of risk gets increased

Ex. Colorectal cancer, breast cancer

What percentage are tumors associated with cancer

15%

Tumor viruses

• interferes with gene regulation through integration of their genome into DNA

• May introduce an oncogene, disrupt a tumor suppressor genes or convert protooncogene to oncogene

Viral proteins can…

Inactivate p53 and other tumor suppressor proteins which deregulates cell cycle receptors

2 types of tumors

Benign tumors - non cancerous as they dont invite surrounding tissues or migrate to other sites of the body

• Can potentially turn cancerous or not

• Can grow teeth, lashes etc

Malignant tumor - cancerous, they continue to grow and invade surrounding tissues and spread to new sites (metastasize)