Genetic Basis of Development

1. Genetic Basis of Development

2. Eukaryotic Genome Organization Prokaryotic cell vs Eukaryotic cell

3. 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

4. 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

6. 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

7. 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

8. So how does a cell decide?

9. 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

10. 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

11. 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

12. 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

13. Apoptosis During Development • Apoptosis – programmed cell death; important during embryonic development • Example: • Tissues between fingers and toes dies off in utero (called morphogenesis)

14. 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

15. 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