Biology Reference
In-Depth Information
Chapter 11
Transcriptional Network Logic: The
Systems Biology of Development
Isabelle S. Peter and Eric H. Davidson
Division of Biology, MC 156
e
29, California Institute of Technology, Pasadena, CA 91125, USA
Chapter Outline
Development is a System-Wide Direct Output of the
Genome 213
GRN Structural Components and Model Representation 214
The Regulatory State Concept 215
System-Wide and Deep Information Flow in Development 216
General Features of the Developmental Process 217
Developmental GRN Dynamics 221
Examples of GRN-Mediated Spatial Control in Development 222
Endomesoderm Development in
Example 2: Double-Negative Gate Circuitry for Spatial
Restriction of the Skeletogenic Cell Fate 222
Example 3: Signaling and Cell Fate Specification 223
Example 4: Parallel Mechanisms in Cell Fate Initiation 224
Example 5: Mechanism of Irreversibility in the
Developmental Process
224
Example 6: GRN-Mediated Cell Fate Decision
224
Conclusion: The Explanation of Development
224
S. purpuratus
Embryos
222
Note added in proof
226
Example 1: Use of Maternal Anisotropy to Define
a Zygotic Regulatory Compartment
Acknowledgement
226
222
References
226
How are the operations of development so coordinated as to give
rise to a definitely ordered system? It is our scientific habit of
thought to regard the operation of any specific system as deter-
mined primarily by its specific physical-chemical composi-
tion
.
.This mechanistic assumption implies some specific
structure or material configuration in the system, and since the
organization of the egg is hereditary, the structure or configura-
tion must be preserved by cell division without loss of its specific
character
.
.
(EB Wilson, The Cell in Development and Heredity, 3rd edn,
1924, p.1115).
required to direct development was already clearly
formulated by the end of the 1880s, on the basis of a large
amount of indirect evidence and logical deduction there-
from (reviewed in refs.
[1,2]
; for modern commentary see
refs.
[3
5]
). Although there was no direct evidence, the
concept of genomic control of development was suffi-
ciently precise by 1889 that Boveri set out deliberately to
provide an explicit direct test of it
[4]
. Though he failed in
this initial attempt, he succeeded only a few years later with
one of the classic systems biology experiments of the early
20th century. This was his famous 1902
e
e
1904 polyspermy
The concepts and precepts of systems developmental
biology are scarcely a recent invention. Once it was real-
ized that the process of development is directly controlled
by the genome (to use the modern word), the basic concepts
of systems developmental biology were directly implied,
just as the quote above illustrates. Wilson had no doubt
whatsoever that the hereditary events of development are
genomically determined, and his 'specific structure or
material configuration in the system', his 'mechanistic
assumptions', have in our time materialized in the form of
the gene regulatory networks (GRNs) that lie at the heart of
systems developmental biology. The idea that the zygote
nucleus carries in its chromosomes the genetic information
experiment, done on sea urchin eggs
[1,6
8]
. Boveri made
use of the unequal distribution of chromosomes resulting
from fertilization with more than one sperm to study the
developmental effects of aneuploidy. When the first four
cells of the embryo were separated and individually
cultured, only those containing a complete set of chromo-
somes produced normally developed larvae, whereas all
other blastomeres experienced developmental failure. The
analysis was quantitative and was replete with a predictive
mathematical model, and it was entirely modern in its
causal experimental logic. Boveri derived two essential
conclusions: first, that the process of embryonic develop-
ment requires the presence (and in some manner the action)
e
