Symposium – Embryonic induction

S04-01

Calfacilitin: A new player in neural induction

Costis Papanayotou1,5, Ping Liao2, Song-Quing Lu3, Lei Zhu6,

Alex Shaw1, Andrea Streit4, Dejie Yu2, Tuck Wah Soong2,3,

Claudio D. Stern1, Guojun Sheng1,7

1University College London, London, United Kingdom2National University of Singapore, Singapore, Singapore3National Neuroscience Institute, Singapore, Singapore4King’s College London, London, United Kingdom5Institut Jacques-Monod, Paris, France6Origen Theraputics, CA, United States7RIKEN Center for Developmental Biology, Kobe, Japan

Although Calcium has been implicated in the specification and

morphogenesis of the neural plate for some time, the mechanism

by which it is regulated and its relationship to the rest of the neu-

ral induction cascade have remained unclear. A molecular screen

for early responses to neural induction in the chick embryo has

uncovered a new player in the neural induction cascade. This is

a gene encoding Calfacilitin, a novel transmembrane Calcium-

channel facilitator that increases intracellular Calcium concentra-

tion both by generating a larger window current and by slowing

the inactivation of the L-type Cav1.2 Calcium channel. Calfacilitin

controls neural plate formation by regulating the expression of

Geminin and Sox2. Morpholino-mediated knockdown of Calfacil-

itin causes failure of Sox2 expression and neural plate develop-

ment, which can be rescued merely by increasing intracellular

Calcium. These results help us to place Calcium signalling in a

cascade of events during neural plate development and also

uncover a new player in the modulation of Calcium transport.

doi:10.1016/j.mod.2009.06.1058

S04-02

How many ways to make a chordate: Comparison of the devel-

opmental programmes of ascidians and vertebrates

Daniel Sobral, Andrea Pasini, Patrick Lemaire

Institute for Developmental Biology of Marseille-luminy, Marseille,

France

Tunicates, including ascidians are the closest living relatives

of vertebrates, with whom they share a tadpole-like larval form.

At the morphological and embryological level, however, verte-

brates share structures and processes that have been lost in asci-

dians. For example, tail extension in ascidians relies on cell

rearrangements and intercalation, rather than on the growth of

a tailbud as in vertebrates. More generally, the ascidian stereo-

typed embryogenesis departs from that of vertebrates, as it is

based on an invariant cell lineage.

We are trying to understand how chordates can form similar

tadpole-like larvae in spite of apparently different developmental

strategies. We have addressed this question by quantifying the

extent of divergence of gene expression profiles between ortho-

logs from Ciona intestinalis and the teleost fish Danio rerio. We

found a surprisingly high level of divergence at all stages, includ-

ing the phylotypic stage. This extent of divergence was similar for

developmental regulators and their effectors, but differed

between tissues. The muscle program was best conserved in spite

of the lack of somites. Surprisingly, we found that a complex

genetic program similar to that found in vertebrates to regulate

the formation of successive somites acts along the ascidian tail,

but has been recruited for A/P epidermal patterning.

doi:10.1016/j.mod.2009.06.1059

S04-03

Dynamic patterning of the vertebrate neural tube

Ana Ribeiro, Eric Dessaud, Yan Gu, Dan Zhu, James Briscoe

National Institute for Medical Research, London, United Kingdom

Like most developing tissues, the assembly of the central ner-

vous system depends on the patterned generation of different cell

types during embryogenesis. In ventral regions of the neural tube,

the graded activity of Sonic Hedgehog (Shh) controls the spatial

organization of neuronal subtypes along the dorsoventral axis.

This pattern of neurogenesis is established dynamically with

the progressive generation of distinct domains of progenitors that

produce the different ventral neurons. These progenitor domains

are delineated by the expression of combinations of transcription

factors. Even though there is increasing knowledge of how Shh

directs the differential expression of the transcription factors that

mark the progenitor domains, it is still not clear how the patterns

of expression acquire their exquisite precision. To gain insight

into the mechanisms involved in this process we are developing

software that will produce a spatiotemporal atlas of progenitor

markers expression in the neural tube. Using a preliminary ver-

sion of this software we have began to document and analyze

the dynamics and reliability of neural patterning in embryos.

We are also starting to characterize the role of Shh in regulating

the spatial changes in progenitor domain patterning over time.

Moreover, these data allow us to address the extent and signifi-

cance of cell-to-cell variability during pattern formation. Together

these approaches will provide insight into how the remarkable

M E C H A N I S M S O F D E V E L O P M E N T 1 2 6 ( 2 0 0 9 ) S 2 8 – S 2 9

ava i lab le at www.sc iencedi rec t .com

journal homepage: www.elsevier .com/ locate /modo

precision in pattern formation is achieved in the developing neu-

ral tube.

doi:10.1016/j.mod.2009.06.1060

S04-04

Mechanisms regulating differentiation onset in the embryonic

axis and ES cells

Barry J. Collins, Isabel Olivera-Martinez, Marios P. Stavridis,

Kate G. Storey

University of Dundee, Dundee, United Kingdom

During development of the vertebrate embryo neuronal differ-

entiation and neural patterning take place progressively as the

spinal cord is generated and the body axis elongates. Fibroblast

Growth Factor (FGF) signalling maintains the undifferentiated cell

state of axial progenitor cells in the stem zone/tailbud. As cells

leave this region they encounter retinoic acid (RA), provided by

the segmenting paraxial mesoderm, which now inhibits FGF sig-

nalling and drives differentiation. Here we present data demon-

strating the conservation of this FGF/RA differentiation switch

throughout body axis extension and reveal how this is elaborated

in the tail bud to arrest elongation and so define body axis length.

Analysis of mouse embryonic stem (ES) cell differentiation indi-

cates that following a period of endogenous FGF activity, which

is required for loss of self-renewal, RA also acts by attenuating

FGF signalling to drive neural differentiation. However, exposure

to retinoic acid or blocking FGFR signalling can also accelerate

non-neural ES cell differentiation. These findings indicate that

the FGF/RA switch is a conserved and generic signalling mecha-

nism mediating differentiation progression in embryos and ES

cells.

doi:10.1016/j.mod.2009.06.1061

S29M E C H A N I S M S O F D E V E L O P M E N T 1 2 6 ( 2 0 0 9 ) S 2 8 – S 2 9