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Gene Regulatory Networks
and the Evolution of
Animal Body Plans
Eric H. Davidson, Douglas H. Erwin
Science 2002, 295:1669 (2002)
National Academy of Sciences, April 5, 2005; 102
侯紹敏
李懿瑋
游竣評
郭嫚茜
張凱迪
中央大學 系統生物與生物資訊研究所
1
Outline
• Development of the animal body plan
• Different rate in the evolution
• Developmental GRNs features and four
components
• How GRNs explain changes of the
evolution
• Summery
2
Body plan
• blueprint
• symmetry, # of body segments and #
of limbs
• tube-within-a-tube vs. sac-like
• triploblasty
http://users.tamuk.edu/kfjab02/Biology/Introzoology/b1313_ch16.htm
3
triploblasty
Baer's laws for embryology:
Two rules from four
1. The general characters of
the group to which an
embryo belongs appear in
development earlier than
the special characters.
2. The less general structural
relations are formed after
the more general, and so on,
until the most specific
appear.
4
Schematic representation of
sea urchin embryo development
P. Oliveri, E. H. Davidson, Curr. Opin. Genet. Dev. 14, 351(2004).
5
顯生宙
4700 ma
冥古代
Major diversification of life in the Cambrian
Explosion. Many fossils
Marinoan glaciations
Possible "snowball Earth" period.
Followed by Good fossils of multi-celled animals.
oxygen levels in the atmosphere increased
元古宙
太古宙
630~8
50 ma
http://en.wikipedia.org/wiki/Geologic_time_scale
6
Relationship
Body plans dev
Different combination of
TF, cis-regulatory module
Temporal , spacial
GRN
GRN structure is inherently hierarchical, because each
phase of development has beginnings, middle stages, and
progressively more fine-scale terminal processes.
7
Gene regulatory network
Regulatory genes
cis-regulatory modules
linkages
cis-regulatory modules:
eg. enhancer, silencer , insulator
> 300bp
> 10 binding sites
> 4 transcription factors
8
"Box-and-arrow" diagrams
intercellular
component
transcription
repess
Known
sequence
P. Oliveri, E. H. Davidson, Curr. Opin. Genet. Dev. 14, 351(2004).
9
Sea urchin VS. Starfish
Kingdom: Animalia
Phylum: Echinodermata
Class: Echinoidea
Kingdom: Animalia
Phylum: Echinodermata
Class: Asteroidea
10
Kingdom
biological classification
From Wikipedia
11
Q1: why So little change in phylumand superphylum-level body plans
since the Early Cambrian? Like
Tetrapod, segmented.
Q2: why Great changes have
subsequently occurred within phyla
and classes?
12
GRN Components
• Kernels - inflexible, upstream
• plug-ins – repeatedly coopted
• Switch - I/O devices
• gene batteries
13
Kernels
• consist of regulatory genes
• to specify the spatial domain
• given developmental functions
• particular form - recursive wiring
• Interference with expression->
destroy kernel function altogether
14
switch
plug-in
plug-in
kernel
2
3
4
switch
Gene batteries
15
Echinoderms endoderm
• a gene regulatory feedback loop
• all except delta are regulatory
genes
• highly recursive
• phase
endoderm(yellow)
mesoderm(gray)
• surrounded by
other network
linkages that are
not conserved
EH Davidson and DH Erwin. Science 2002, 295:1669 (2002)
16
developmental processes for the heart
• the linkages are also
highly recursive.
• eg. the nkx2.5, tbx,
mef2c, and gata4
genes all receive
inputs from multiple
other genes of the
kernel, as do the tin,
doc, mid, pnr, and
mef2c genes of the
Drosophila network.
EH Davidson and DH Erwin. Science 2002, 295:1669 (2002)
17
Additional examples
• Anterior to posterior and midline to
lateral specification of the nervous
system
• Eye field specification
• Gut regionalization
• Development of immune systems
• Regionalization of the hindbrain and
specification of neural crest
18
Plug-ins
• Structurally conserved
• used within and among species
• not dedicated to formation of given body
parts, providing inputs into regulatory
apparatus
• eg. affecting a confined repertoire of
transcription factors, are used
repeatedly, often acting as dominant
spatial repressors in the absence of
ligand and as facilitators of spatially
confined expression in its presence.
19
Hedgehog signal
• Wnt
• Transforming
growth factorB
• Fibroblast
growth factor
• Hedgehog
• Notch
• Epidermal
growth factor
• Flexible
• Homologous processes in related animals
• Evolutionarily very labile
K. M. Cadigan, R. Nusse, Genes Dev. 11, 3286 (1997).
20
Gene batteries
• Only deployed at the end of this
process
• structural genes :protein-coding
genes
• the products of which execute cell
type–specific functions
• Differentiation gene batteries display
inherent evolutionary lability and
undergo continuous renovation
21
Gene batteries properties
Outputs terminate the network
at the periphery of developmental
GRNs
• Control the progressive formation of
spatial patterns of gene expression
22
switch
• may be regulating other network
subcircuits
• appear to be responsible for many
kinds of evolutionary change in
developmental process
Eg. Cell cycle control
hox gene ->direct repressive on
expression of wing-patterning genes
-> morphology
23
Predicted Evolutionary Consequences of
Changes in GRN Architecture
Change in them is
prohibited
Once GRNs kernels
assembled since
Cambrian ,they
could not be
disassembled!
The most frequent
and least
constrained
EH Davidson and DH Erwin. Science 2002, 295:1669 (2002)
24
• Micro evolutionary thinking->
Temporally homogeneous way
intersects with mechanisms of GRN
change
• Comparative molecular->
the evolutionary point of origin
25
• GRNs of subsequent adaptational
change is forced to lower since
Cambrian.
• Early assembly of kernels, plug-in
and switch, AND piecemeal alteration
of gene batteries provide evolution.
• The conserved kernels of extant
developmental GRNs is the answers
26
Summery
cis-regulatory DNAs
execute
The program for development
regulate
transcription factors
components of cell signaling
pathways
classes of GRN componen
•
•
•
•
kernels
plug-ins
Switch
gene batteries
27
References
• M. Levine, E. H. Davidson, Proc. Natl. Acad. Sci.
U.S.A.102, 4936 (2005).
• P. Oliveri, E. H. Davidson, Curr. Opin. Genet. Dev. 14,
351(2004).
• http://strc.herts.ac.uk/bio/maria/Projects.htm
• W. J. R. Longabaugh, E. H. Davidson, H. Bolouri,
Dev.Biol. 283, 1 (2005).
28
• Thank you!!
29