Download Chapter 21. Development of Multicellular Organisms Sydney

Chapter 21. Development
of Multicellular Organisms
Sydney Brenner, 1960
Mutation vs. variation
Mutation
Variation
Mutation
Types of mutation
1. No phenotype
-Amorph
2. Loss of function
-Null
-Hypomorph
3. Gain of function
-Hypermorph
-Antimorph (dominant negative)
1. Robust model for the behavior of individual and identified
cells 1000 somatic + 1000-2000 germ cells
2. Convenient model for genetics  Single heterozygote
worm can produce homozygous progeny
3. Cell fates and lineages are almost perfectly predictable
Mechanisms for C. elegans
development
• Polarity formation by maternal effectors
• Cell-cell interactions to make complex
patterns
• Heterochronic genes
• Apoptosis
1. Maternal effect genes
• mRNA from mother is asymmetrically distributed
along anteroposterior axis
Par (partitioning defective) genes bring
P granules to posterior pole
One cell having P granule give rise to germ cells
2. Cell-cell interactions to make
complex patterns
2. Cell-cell interactions to make
complex patterns
• P2-EMS interaction:
1. Mom mutants without gut
-Mom gene (Wnt) expressed in P2 cell
-Frizzled gene (Wnt receptor) expressed
in EMS cells
2. Pop mutants with extraguts
-Pop genes encode LEF-1/TCF homolog
-Reduced pop activity  gut
-Increased Pop activity  muscle
Cells change over time in their
responsiveness to signals
• At four cells
Anterior cell specification  depend on Notch
signals
• At 12-cell stage, both Aba and Abp progenitors
exposed to Notch signals
 Granddaughter of Aba cells induce pharynx
 Granddaughter of Abp cells unresponsive to
Notch
Heterochronic genes control the
timing of development
• Heterochronic phenotypes:
The cells in a larva of one stage behave as
though they belong to a larva of a different
stages, or cells in the adult carry on
dividing as though they belonged to a
larva
• lin-4 for the transition larval stage1  3
• let-7 for the transition late larva  adult
Apoptosis
• 1030-131
• Cell death abnormal gene
-ced-3, ced-4, egl-1 (caspase, Apaf-1,
BAD homolog)  cause cell death
-ced-9 (Bcl-2 homolog)
 repress cell death
The Nobel Prize in Physiology or Medicine 2002
"for their discoveries concerning 'genetic regulation of organ
development and programmed cell death'"
Sydney Brenner
1/3 of the prize
H. Robert Horvitz
1/3 of the prize
John E. Sulston
1/3 of the prize
United Kingdom
USA
United Kingdom
The Molecular
Sciences Institute
Berkeley, CA, USA
Massachusetts
Institute of
Technology (MIT)
Cambridge, MA,
USA
The Wellcome Trust
Sanger Institute
Cambridge, United
Kingdom
b. 1927
(in Union of South
Africa)
b. 1947
b. 1942
Drosophila and the molecular
genetics of pattern formation:
Genesis of the body plan
Seymor Benzer
Overall procedures
Overall procedures
Syncytial Specification
Pole cells
Maternal effects
• Egg polarity determination
• A-P and D-V axis
Cytoplasmic bridges
Egg polarity genes
(Maternal effectors)
Egg polarity genes
(Maternal effectors)
Dorsoventral axis
Dorsal protein (NF-kB):
-Dorsally, the protein is present in
the cytoplasm and absent from the
nuclei; ventrally, it is depleted in the
cytoplasm and concentrated in the
nuclei.
-Toll gene controls the redistribution
Dorsoventral specification
Dorsal protein concentration
High  activate twist, repress dpp (decapentaplegic)
Intermediate  sog (short gastrulation)
Dorsolventral specification
Fate map
• Distribution of twist in mesodermal cells
Anteroposterior specification
• Maternal genes, bicoid, nanos
• Segment genes refine the pattern
–
–
–
–
Zygotic genes
Six gap genes: Coarse subdivision
Pair rule genes: Segment alteration
Segment-polarity genes:
Homeotic selector genes
Anteroposterior specification
• Krupel lacks 8 segments (T1-A5)
• Even-skipped (eve) lacks oddnumbered parasegments
• Fushi tarazu (ftz) lacks even-numbered
parasegments
• Gooseberry posterior half is the mirror
image of anterior half
Pair rule genes
• Formation of parasegments
• Expression pattern of ftz (brown) and
eve (gray)
Segment polarity genes
• Forms parasegments
polarity
• Involves cell-cell
interactions
• Associated with two
signaling pathways
– Wnt
– Hedgehog
Regulatory hierarchy
The Nobel Prize in Physiology or Medicine 1995
"for their discoveries concerning the genetic control
of early embryonic development"
Edward B. Lewis
1/3 of the prize
Christiane
Nüsslein-Volhard
Eric F. Wieschaus
1/3 of the prize
1/3 of the prize
USA
Federal Republic of
Germany
USA
California Institute
of Technology
Pasadena, CA, USA
Max-Planck-Institut
für
Entwicklungsbiologi
e
Tübingen, Federal
Republic of
Germany
Princeton University
Princeton, NJ, USA
b. 1918
d. 2004
b. 1942
b. 1947
Homeotic mutations
Homeotic selector genes
• Hox gene complex
– Antennapedia complex
– Bithorax complex
• Contain homeodomain
– 60 amino acids
– DNA binding region
• Regulate positional information
Hox gene complex
Expression of hox gene complex
Hox gene complex
Comparison of hox gene
expression
Comparison of hox gene
expression
Organogenesis and patterning of
appendage
• Methods in fly genetics: Somatic mutations
Mosaic
• Methods in fly genetics: Enhancer trap
Imaginal discs
• Groups of cells
set aside
undifferentiated
• 19 discs (9 pairs
+ 1 genital)
• Develop into
organs such as
leg, wing, eyes
etc.
Specific ID genes define organs
• Distal-less  expressed in appendages
• Pax-6  expression in eyes
Wing formation
• Sector
formation in
wing disc
• Four
compartments
foms
• engrailed,
apterous genes
are involved
Wing formation
Wing formation
(A) The shapes of marked
clones in the Drosophila
wing reveal the existence of
a compartment boundary.
The border of each marked
clone is straight where it
abuts the boundary. Even
when a marked clone has
been genetically altered so
that it grows more rapidly
than the rest of the wing
and is therefore very large, it
respects the boundary in the
same way (drawing on right).
Note that the compartment
boundary does not coincide
with the central wing vein.
(B) The pattern of
expression of the engrailed
gene in the wing, revealed
by the same technique as
for the adult fly shown in
Figure 21–40. The
compartment boundary
coincides with the boundary
of engrailed gene
expression.
Limb formation
Bristle formation
• achaete, scute genes
-HLH
-Proneural genes
Scute expression in wing disc
Lateral inhibition
• Notch-delta
Lateral inhibition
Notch somatic mutation
Loss of lateral inhibition
Bristle patches
Bristle formation
• Numb gene
-Block Notch gene activity
Bristle formation
• Planar polarity genes
• Orienting bristle backward position
• frizzled proteins  control planar polarity
• dishevelled  downstream of frizzled
Bristle formation