The elucidation of the complete genome sequences of

various model organisms, in conjunction with the development

of new screening methods, provides a type of functional

genomics that has been unavailable to developmental

biologists in the past. The collaboration between novel computational

and molecular biological techniques and traditional

embryology was evident in the outstanding research

presented at the annual meeting of the Society for Developmental

Biology held in San Francisco this summer. The

underlying theme of the meeting was how a partnering

between different disciplines can be extremely fruitful in

enabling both gene discovery and the understanding of how

genes work in concert to carry out developmental processes

Taneyhill, Lisa A.

Caltech Authors - Main

Genome Biology 2005, 6:359
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Meeting report
Understanding embryonic development: from screens to genes
Lisa A Taneyhill
Address: Division of Biology, California Institute of Technology, Pasadena, CA 91125, USA. E-mail: ltaney@caltech.edu
Published: 24 November 2005
Genome Biology 2005, 6:359 (doi:10.1186/gb-2005-6-12-359)
The electronic version of this article is the complete one and can be
found online at http://genomebiology.com/2005/6/12/359
© 2005 BioMed Central Ltd 
A report on the 64th Annual Meeting of the Society for
Developmental Biology, San Francisco, USA, 27 July-
1 August 2005.
The elucidation of the complete genome sequences of
various model organisms, in conjunction with the develop-
ment of new screening methods, provides a type of func-
tional genomics that has been unavailable to developmental
biologists in the past. The collaboration between novel com-
putational and molecular biological techniques and tradi-
tional embryology was evident in the outstanding research
presented at the annual meeting of the Society for Develop-
mental Biology held in San Francisco this summer. The
underlying theme of the meeting was how a partnering
between different disciplines can be extremely fruitful in
enabling both gene discovery and the understanding of how
genes work in concert to carry out developmental processes.
Highly pertinent to this theme were discussions about RNA
interference (RNAi) screening. Julie Ahringer (Wellcome
Trust/Cancer Research UK Gurdon Institute, University of
Cambridge, UK) discussed the work in her laboratory that
uses genome-wide RNAi screening to understand the molecu-
lar basis of cell polarity in the nematode Caenorhabditis
elegans, in which RNAi is readily achieved by feeding worms
with bacteria containing DNA sequences encoding interfering
RNAs. Using an RNAi library consisting of 16,757 such bacter-
ial strains, covering 86% of the C. elegans genome, Ahringer’s
group has identified 1,722 genes with an RNAi phenotype
(1,200 of which are novel) by performing a dissecting micro-
scope screen for worms showing lethality, abnormal morphol-
ogy or movement, or slow growth. The lethal mutants isolated
in this first screen were subsequently examined for various
polarity defects, and 541 out of 945 lethal genes were identi-
fied that fit these criteria. Two of these genes, chp-1 and CK1
(encoding casein kinase 1), are involved in spindle position
and orientation. chp-1 is also known to function in maintain-
ing the balance between anterior and posterior PAR
(partitioning-defective) proteins. CHP-1 normally localizes to
the cytoplasm and is thought to play a role in degrading those
PAR proteins with anterior localization; the chp-1 RNAi phe-
notype shows symmetric cell division. The CK1 RNAi pheno-
type leads to the production of an asymmetric, unstable
spindle such that both pronuclei go to the anterior end of the
cell. Casein kinase 1 normally localizes to the asters and has a
punctate distribution in the cytoplasm, helping to position the
spindle through forces that involve the activity of the
G-protein regulators GPR-1 and GPR-2 (GPR1/2). CK1 func-
tions upstream of phosphatidylinositol-4-phosphate 5-kinase
(PPK-1), a protein that generates phosphatidylinositol diphos-
phate (PIP2) through the phosphatidylinositol signaling
pathway. Ahringer described how RNAi against both GPR-1/2
and CK1 showed that GPR-1/2 works in a signaling cascade
with CK1 and PPK-1 to allow the asymmetric localization of
PIP2, which is required for the maintenance of both PAR
asymmetry and spindle position. Taking the broader view, her
laboratory has generated a unique RNAi library to facilitate
new genome-wide screens for other phenotypes.
Many laboratories have been working on defining stem cells
in various organisms, and how the stem-cell niche influences
the process of self-renewal. Minx Fuller (Stanford Univer-
sity, USA) described how, using Drosophila spermatogenesis
as a model system, she and her colleagues have identified the
ligand Unpaired (Upd) as a protein secreted by the stem-cell
niche, a specialized environment consisting of ten support
cells that maintains the Drosophila stem cell in the testis.
Upd in turn activates the JAK/STAT signaling pathway in
the male germline, the downstream targets of which regulate
the self-renewal property of stem cells. Using DNA micro-
arrays, a screen was carried out to compare a strain that
ectopically expresses upd and a wild-type strain in an attempt
to identify genes upregulated by JAK/STAT signaling in the
stem cells. In this system, 175 genes were found to be upregu-
lated, 15 of which have predicted STAT consensus binding
sites upstream or within the first intron, as defined by the
program Target explorer [http://trantor.bioc.columbia.edu/
Target_Explorer]. One of these genes, lola, which has at
least 20 splice variants, is expressed ubiquitously in early
germ cells (but not in the hub), and is required to act within
the germ cells for maintenance of the male germline. Thus,
clones of male germline cells that do not express lola lose
their stem cells over time, as the cells differentiate along the
path of spermatogenesis and lose their ability to self-renew.
lola is similar to the mouse plzf gene, which is required for
the maintenance of germ cells in adult males.
The use of comparative genetics and genomics has been par-
ticularly successful in elucidating the evolution of new traits
in vertebrates, a point highlighted by David Kingsley (Stan-
ford University, USA). Evoking the theme of understanding
genes and the processes they regulate, Kingsley reported
work being done in his laboratory using the three-spine
stickleback as a model organism to determine what geno-
typic changes are required to achieve major phenotypic
changes, and whether these changes are dominant or reces-
sive, or in coding or regulatory regions. One such trait is that
of armored plates, as ocean sticklebacks have 36 plates
(high-plate sticklebacks), while their freshwater counter-
parts have far fewer (low-plate sticklebacks). The Kingsley
lab has found a genomic region that is responsible for 80%
of the variation observed in armored-plate number, and
through a chromosome walk using BAC clones and a com-
parison of microsatellite markers, they have identified the
ectodysplasin (EDA) gene as a possible candidate for con-
trolling armored plate formation. This gene gets its name
from the condition resulting from mutations in the human
EDA gene result called ectodermal dysplasia, in which the
affected individual has sparse hair and other defects in hair,
teeth and sweat glands. In another fish, the medaka, a muta-
tion in the gene for the ectodysplasin receptor (EDAR)
renders the fish scaleless. To gain further evidence of the
involvement of EDA in armored plate formation, a mouse
EDA cDNA clone was injected into the eggs of low-plate
sticklebacks. The resulting transgenic fish formed plates in
the middle and tail regions, which normally lack such struc-
tures (Figure 1). EDA is involved in a tumor necrosis factor
(TNF)-type signaling pathway in humans and mice, and
mutations in the ligand (EDA), the receptor (EDAR) or the
adaptor protein Edaradd give similar phenotypes. In addi-
tion, the mutation that gives low numbers of armored plates
is in the cis-regulatory region of the EDA gene. Similar
studies using ocean and freshwater sticklebacks have also
been conducted by the Kingsley laboratory to understand the
loss of the hindlimb in the freshwater stickleback. 
Winding up the meeting, John Gerhart (University of Cali-
fornia, Berkeley, USA) highlighted the origin of chordates
through a comparison between chordate gene expression
and that in the hemichordate Saccoglossus kowalevskii.
Hemichordates are strikingly similar to chordates in that
they are bilaterally symmetrical, have structures analogous
to gill slits and a post-anal tail, but they have no real dorsal
hollow nerve cord. Instead, the nervous system is highly
diffuse, with a dorsal-ventral axon tract and an outer body
layer full of nerves. Orthologs to 41 neural patterning genes
in chordates were identified as having similar anterior-pos-
terior expression mappings in hemichordates, with Wnt1
and Fgf8 being found at the level of the first gill slit in hemi-
chordates compared to the midbrain-hindbrain junction in
chordates. Thus, comparisons can be made between the
marker genes identifying the brain and spinal cord struc-
tures in chordates and their distribution along the anterior-
posterior axis in hemichordates. 
Gerhart described his group’s findings that the stomochord,
a structure found in Saccoglossus, and the notochord are not
homologous structures, as the stomochord expresses molec-
ular markers similar to prechordal endomesoderm. More-
over, Gerhart’s group has found that patterning along the
dorsal-ventral axis in Saccoglossus occurs through a bone
morphogenetic protein (BMP)-chordin gradient, but that
this gradient is inversely oriented in comparison to chor-
dates: the dorsal midline in hemichordates expresses BMPs,
while the ventral midline expresses chordin. In a remarkable
experiment, exogenous BMP added to the water in which
hemichordate fertilized eggs are kept resulted in the radial
expansion of genes that are normally expressed only in the
dorsal midline and in the loss of the mouth structures (a
ventral structure) in the developing embryos. Conversely,
when BMP expression was suppressed by small interfering
RNAs at the fertilization stage, this resulted in the expansion
of the ventral domain, coupled with an enlargement of the
mouth and the eventual elimination of the entire head struc-
ture. From these experiments the researchers concluded that
many aspects of anterior-posterior patterning have been
conserved in hemichordates and chordates, but that there
was an alteration in dorsal-ventral patterning in the chor-
359.2 Genome Biology 2005, Volume 6, Issue 12, Article 359 Taneyhill http://genomebiology.com/2005/6/12/359
Genome Biology 2005, 6:359
Figure 1
Arming the stickleback. Introduction of mouse ectodysplasin cDNA into
(a) low-plate sticklebacks yields (b) transgenic fish with an increased
number of armored plates. Adapted with permission from Colosimo et al.:
Science 2005, 307:1928-1933.
(a)
(b)
date lineage, leading to the centralization of the nervous
system and the development of a notochord. 
The meeting showed that a more interdisciplinary approach
to developmental biology that couples traditional embry-
ological approaches with molecular biology and computa-
tional techniques has allowed us to understand, at a
molecular level, the role of various genes and the products
they regulate during different developmental processes. We
look forward to more results from these collaborative efforts
emerging over the next year, and to hearing about them at
the next annual meeting of the society at the University of
Michigan, Ann Arbor, in 2006.
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http://genomebiology.com/2005/6/12/359                                                          Genome Biology 2005, Volume 6, Issue 12, Article 359 Taneyhill  359.3
Genome Biology 2005, 6:359


Understanding embryonic development: from screens to genes

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Understanding embryonic development: from screens to genes

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