Chapter 16: Development, Stem Cells, and Cancer

Giving rise to an organism:

Cell Division (how? Ch. 9 & 10) Cell Differentiation (why? Ch. 14,15,16) Morphogenesis (what? Ch. 16 & 18)

Cell Differentiation 1. Cytoplasmic Determinants

- RNA present? - proteins? - cytoplasm amount?

2. Cell Environment - anchorage dependent - cell-surface molecules - growth factors

Specialized signal transduction: induction – gives rise to specific signals (tissue-specific proteins)

determination – once a cell is committed it doesn’t look back

Determination ≠ Differentiation

Morphogensis *pattern formation (body plan) *positional information (body axes) Bilateral Anterior Posterior Dorsal Ventral

Lewis, Nüsslein-Volhard, Wieschaus Nobel Prize 1995

Lewis: homeotic genes (hox genes) Nüsslein-Volhard & Wieschaus: embryonic lethals - mutations w/phentoypes causing death before breeding maturity

Axis Plan -maternal effect plan/egg-polarity genes - *1 for anterior/posterior *1 for dorsal/ventral *if mutant in mom, offspring mutant *morphogengradients – where & how many -bicoid: two-tailed “butt-head”

Cloning & Stem Cells - Developing a whole organism from a

single cell (genetically identical to parent) totipotent – dedifferentiate then start over & specialize

Dolly CC Carbon Copy

• Nuclear transplantation of mammary cells

• Took several hundred embryos for 1 sheep

• Genetically identical to egg donor

• Only lived 6 years due to lung disease usually found in much older sheep

• Genetically identical but phenotypically different

• X inactivation

Why would cloning be faulty?

Epigenetic changes

which is?

Acetylation of histones

which is?

DNA methylation

which is?

Hmmm…do we need to go over those again?

Stem Cells

Embryonic

• Blastocyst (ball of 100 cells)

• Can give rise to all cell types (pluripotent)

• Only way to obtain is from human embryos (ES)

Adult

• Can give rise to many cell types but not all

• Ex: bone marrow

• Since 2007 can use induced pluripotent stem cells (iPS)

Abnormal Gene Regulation Proto-oncogenes –code for normal cell growth & division Oncogenes – caused from: ^movement of DNA within the genome (translocation) ^amplification of a proto-oncogene (duplication) ^mutation of proto-oncogene (point mutation) p. 325

ras proto-oncogene

- named for rat sarcoma

- causes about 30% of human cancers

- G protein for growth factor receptors on PM to cascade of protein kinases

- hyperactive that allows for cascade w/out growth factor

- p. 325

Activity of a tumor suppressor in skin cells. A microscopic image shows three skin cells. In each of them the Cyld protein (green) is situated around the nucleus (blue) and prevents oncogene Bcl-3 from entering. The red structure is the cell's cytoskeleton. (Image: Max Planck Institute of Biochemistry)

Tumor-suppressor genes inhibit cell division

^repair damaged DNA

^control anchorage

^inhibit cell-signaling

Apoptosis: ^programmed cell death ^break down cell ^put pieces in vesicles called “blebs” ^nearby cells ca phagocytize safely

Ch. 18 – Genomes and Their Evolution

Genomics – the study of whole sets of genes & their interactions

Bioinformatics – high-throughput

Whole-genome shotgun approach (fig.18.2 p. 344)

Metagenomics –

from a group of species

National Center for Biotechnology Information (NCBI)

www.ncbi.nlm.nih.gov - Contribute to GenBank (database of

sequences) - Controls BLAST: ^DNA sequences ^protein sequences ^aa sequences for function

Proteomics – the study of full protein sets (proteomes) encoded by genomes Systems Biology – look at the whole system in terms of its parts

Cancer Genome Atlas – sequenced lung, ovarian, glioblastoma

1990-2012: - 3700 genomes completed - 7500 genomes & 340 metagenomics started - only 183 are eukaryotic

How to Look at Genomes Genome Size

Number of Genes Gene Density & Noncoding DNA

Table 18.1 p. 348

Pseudogenes – former genes w/too many mutations

1. Transposable Elements 2. Repetitive DNA 3. Simple Sequence DNA 4. Introns 5. Multigene Families

1. Transposable Elements (jumping genes)

Transposons – transposase will cut & paste or copy & paste on the DNA Retrotransposons – reverse transcriptase copies RNA, makes DNA then pastes in the DNA

“If you know you are on

the right track, if you

have this inner

knowledge, then nobody

can turn you off…no

matter what they say.”

2. Repetitive DNA – mistakes during DNA replication & recombination (long segments)

3. Simple Sequence DNA – short segments (fewer than 15 nucleotides) STR – short tandem repeat (2-5 nucleotides)

4. Introns

5. Multigene Families – identical DNA sequences ex: Hemoglobin or rRNA for ribosomes

Evo-devo (Evolutionary Developmental Biology)

Read p. 357-361