Transcript Genes & Development

Genes & Development
Part 1: The Debate
Gene Theory
Nuclear vs Cytoplasmic Inheritance
Is control over development tied to the nucleus
(chromatin) or to the cytoplasm?
T Boveri & EB Wilson – Nuclear control
TH Morgan – cytoplasmic control
Gene Theory
Boveri’s support for nuclear control
Polyspermy in sea urchins
• Embryos developing with multiple sets of
chromosomes had defects
• Chromosome number (nucleus) important
Gene Theory
EB Wilson & Nettie Stevens
Correlated chromosome absence/presence with
sex determination
• Drosophila
XO & XY = male
XX = female
Gene Theory
 TH Morgan
 Chief proponent of cytoplasmic inheritance
 1910 his lab accumulated data that supported
chromosomal inheritance
 Discovered and characterized Drosophila white (w)
mutant (has white eye)
 w phenotype had sex linked inheritance pattern –
• w male x wt female  F1 all wt offspring
• wt male x F1 female  only w-eyed males
Gene Theory
Morgan’s conversion
Since mutation was inherited together with the
X chromosome, Morgan accepted the
chromosomal inheritance theory
wholeheartedly
Went further to hypothesize that genes were
arranged linearly on chromosomes
Gene Theory
Nettie Stevens was a graduate student with
Morgan at Columbia University
Did postdoctoral studies with Wilson
Wilson and Morgan were very good friends
HOMEWORK: go online to devbio
website and read material at website 4.1
Quiz on Monday!
Geneticist vs Embryologist
Wilson and Morgan were embryologists
Their combined support of the
chromosomal inheritance theory brought
more geneticists into embryological
systems
Influx of geneticists was disdained by
classical embryologists
EE Just, H Spemann, F Lillie et al
Geneticists vs Embryologists
 Embryologists set forth 3 criteria that must be
satisfied by genetics in order to accept the
dominance of the gene theory
1. How can identical chromosomes give rise to
differentiated cell types
2. Demonstrate that genes control early
developmental processes
3. Explain environmentally influenced phenomena
such as temperature dependent sex
determination
Gene Action in Early Development
Brachyury (brachy = short; ury = tail)
Salome Gluecksohn-Schoenheimer
Characterized the early embryos of mice with
the Bra mutant
Adult phenotype – deformed tails/pelvis
Embryo phenotype – lack posterior notochord
Gene Action in Early Development
Drosophila wing mutations
Conrad Waddington
Demonstrated defects in the imaginal disk
formation
Gene Action in Early Development
Both Waddington’s and Gluecksohn’s
experiments established that genes did
effect early developmental processes
1 down 2 to go
Genomic Equivalence
 Explain differential gene expression
1. Establish that genomes of differentiated
cells are equivalent
2. Determine why only certain genes are
expressed
Genomic Equivalence
 Regeneration of newt lens
 Remove lens
 Iris cells trans-differentiate to regenerate the
lens
 Series of changes in iris cells
1.
2.
3.
4.
5.
6.
Ribosome synthesis
DNA replication
mitosis
exocytose melanosomes
form a group of undifferentiated cells
turn on crystalline genes
Genomic Equivalence
Cloning – the ultimate equivalence test
Generate an entire, normal animal from a
the nucleus of a somatic cell
Requires that somatic nucleus is totipotent
Genomic Equivalence
Cloning of the frog Xenopus
laevis by nuclear
transplantation of albino gut
cell nuclei into enucleated, wt
oocytes. All progeny are albino
& female
Genomic
Equivalence
Procedure for cloning frogs
from differentiated nuclei.
Successful cloning requires
serial passage of donor
nuclei through activated
oocytes.
Genomic Equivalence
Enucleate oocyte
Isolate donor nuclei
Inject nuclei into oocyte
Genomic Equivalence
Totipotency of donor
nuclei appears to
decline with age
Genomic Equivalence
Dolly
1st cloned mammal
Mammary epithelial cell
Cultured and maintained in G0
Fused with enucleated oocyte by electric shock
1/434 success rate (0.23%)
Genomic Equivalence
Cloned Mice