Genetic Basis of Development

Eukaryotic Genome Organization

Prokaryotic cell vs Eukaryotic cell

In eukaryotic cells, most DNA is nuclear & organized as follows: dsDNA (helix) is wrapped

around histone proteins which coil together to form nucleosomes

Heterochromatin – sections of DNA where nucleosomes are tightly packed together; little gene expression

Euchromatin – sections of DNA where nucleosomes are more loosely packed; high gene expression

Transcription Factors Within eukaryotes, genes are expressed in a

tissue-specific manner through transcription factors Activators - bind DNA and cause protein-mediated

bending of DNA → transcription occurs Repressors – bind DNA and prevent transcription COMBINATION EXPRESSED AT A PARTICULAR

TIME DETERMINES HOW MUCH PROTEIN IS PRODUCED

Prok vs. Euk regulation of gene expression

Prokaryotes (i.e. bacteria) use operons to regulate gene expression

Eukaryotes use transcription factors Both use regulatory sequences

In prok, the regulatory gene makes repressor In euk, the regulatory sequences are bound by various

transcription factors

Cell Differentiation Cell decides to become a particular type of cell

Cell expresses a particular set of genes that forces it to develop into a particular cell

These tissue-specific genes are located on euchromatin (expressed/loosely wound portion of DNA) within the given cell

So how does a cell decide?

Cells of zygote undergo rounds of mitosis to form stem cells (cells that are not yet differentiated and have the potential to develop into any type of cell)

Based on their location in developing zygote, stem cells produce particular proteins (i.e. transcription factors) which tell the surrounding cells what to become

Transcription Factor “Cascade”

Transcription factor binds with DNA inside nucleus Turns on the expression of particular genes Results in expression of proteins that “cascade” or

spread to neighboring cells Causes those cells in the area to develop into a specific

tissue Embryonic induction – cell will influence (induce)

surrounding cells into developing into particular tissues/organs

Example: SRY gene

Y chromosome contains SRY (sex determining region on Y chromosome) gene

In males, SRY gene produces protein causing differential development of sex organs etc

Example: Cave Fish

“eyeless cave fish” given lens of normal fish → cave fish develops eye sight

Eyeless cave fish lens transplanted into normal fish → nothing happens

Thus there is some factor inside the normal lens that causes it to “induce” surrounding cells to develop into vision-capable cells

Apoptosis During Development

Apoptosis – programmed cell death; important during embryonic development

Example: Tissues between fingers and toes dies off in utero

(called morphogenesis)

microRNA Single stranded RNA (ssRNA) found in all

organisms MicroRNA functions to disrupt mRNA and prevent

it from making proteins Example:

Drosophila mutants without microRNA: the grim, hid, and reaper genes (responsible for apoptosis) are overexpressed → significant uptick in apoptosis and embroyic death

Thus microRNA functions to repress the apoptotic genes in particular tissues

Homeotic Genes Genes found in many organisms that determine

where body parts will go in the organism Ex: HOX genes in drosophila

Mutation in ubx – two thoraxes develop Mutation in antp – leg grow from head