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Team Publications
Epigenetic plasticity and polarity of the embryo
Year of publication 2000
F Janody, J Reischl, N Dostatni (2000 Mar 22)
Persistence of Hunchback in the terminal region of the Drosophila blastoderm
embryo impairs anterior development.
Development (Cambridge, England) : 1573-82
Summary
Anterior terminal development is controlled by several zygotic genes that are positively
regulated at the anterior pole of Drosophila blastoderm embryos by the anterior (bicoid) and
the terminal (torso) maternal determinants. Most Bicoid target genes, however, are first
expressed at syncitial blastoderm as anterior caps, which retract from the anterior pole upon
activation of Torso. To better understand the interaction between Bicoid and Torso, a
derivative of the Gal4/UAS system was used to selectively express the best characterised
Bicoid target gene, hunchback, at the anterior pole when its expression should be repressed
by Torso. Persistence of hunchback at the pole mimics most of the torso phenotype and
leads to repression at early stages of a labral (cap’n’collar) and two foregut (wingless and
hedgehog) determinants that are positively controlled by bicoid and torso. These results
uncovered an antagonism between hunchback and bicoid at the anterior pole, whereas the
two genes are known to act in concert for most anterior segmented development. They
suggest that the repression of hunchback by torso is required to prevent this antagonism
and to promote anterior terminal development, depending mostly on bicoid activity.
F Janody, R Sturny, F Catala, C Desplan, N Dostatni (2000 Jan 15)
Phosphorylation of bicoid on MAP-kinase sites: contribution to its interaction
with the torso pathway.
Development (Cambridge, England) : 279-89
Summary
The Torso signal transduction pathway exhibits two opposite effects on the activity of the
Bicoid (Bcd) morphogen: (i) Bcd function is repressed by Torso (Tor) at the anterior pole of
the embryo leading to a retraction of the expression of many Bcd targets from the most
anterior region of the embryo, where the Tor tyrosine kinase receptor is activated, and (ii)
Bcd function is strengthened by Tor in a broader anterior region, as indicated by a shift of
the posterior border of Bcd targets towards the anterior pole in embryos deprived from Tor
activity. Anterior repression of Bcd targets was not observed in embryos lacking maternal
contribution of D-sor, which acts downstream of Tor and encodes a MAP-kinase kinase. This
indicates that the Ras signalling cascade is directly involved in this process, although the
known transcriptional effectors of the Tor pathway, tll and hkb, are not (Ronchi, E., Treisman,
J., Dostatni, N., Struhl, G. and Desplan, C. (1993) Cell 74, 347-355). Bcd is a good in vitro
substrate for phosphorylation by MAP-kinase and phosphorylation of the protein occur in vivo
on MAP-kinase sites. In the presence of a Bcd mutant that could no longer be phosphorylated
by MAP-kinase, expression of Bcd targets remained repressed by Tor at the pole while
strengthening of Bcd activity was reduced. These experiments indicate that phosphorylation
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Team Publications
Epigenetic plasticity and polarity of the embryo
of Bcd by MAP-kinase is likely to be required for the Tor pathway to induce its full positive
effect on Bcd. This suggests that Tor signalling acts at a distance from the anterior pole by
direct modification of the diffusing Bcd morphogen.
Year of publication 1999
D Niessing, N Dostatni, H Jäckle, R Rivera-Pomar (1999 Apr 15)
Sequence interval within the PEST motif of Bicoid is important for translational
repression of caudal mRNA in the anterior region of the Drosophila embryo.
The EMBO journal : 1966-73
Summary
The Drosophila body organizer Bicoid (Bcd) is a maternal homeodomain protein. It forms a
concentration gradient along the longitudinal axis of the preblastoderm embryo and
activates early zygotic segmentation genes in a threshold-dependent fashion. In addition,
Bcd acts as a translational repressor of maternal caudal (cad) mRNA in the anterior region of
the embryo. This process involves a distinct Bcd-binding region (BBR) in the 3′ untranslated
region (UTR) of cad mRNA. Using cotransfection assays, we found that Bcd represses
translation in a cap-dependent manner. Bcd-dependent translational repression involves a
portion of the PEST motif of Bcd, a conserved protein motif best known for its function in
protein degradation. Rescue experiments with Bcd-deficient embryos expressing transgenederived Bcd mutants indicate that amino acid replacements within the C-terminal portion of
the PEST motif prevent translational repression of cad mRNA but allow for Bcd-dependent
transcriptional activation. Thus, Bcd contains separable protein domains for transcriptional
and translational regulation of target genes. Maternally-derived cad protein in the anterior
region of embryos interferes with head morphogenesis, showing that cad mRNA suppression
by Bcd is an important control event during early Drosophila embryogenesis.
Year of publication 1996
Y Bellaïche, R Bandyopadhyay, C Desplan, N Dostatni (1996 Nov 1)
Neither the homeodomain nor the activation domain of Bicoid is specifically
required for its down-regulation by the Torso receptor tyrosine kinase cascade.
Development (Cambridge, England) : 3499-508
Summary
Bicoid (Bcd) is a maternal morphogen responsible for patterning the head and thorax of the
Drosophila embryo. Correct specification of head structure, however, requires the activity of
the Torso receptor tyrosine kinase cascade, which also represses expression of Bcd targets
at the most anterior tip of the embryo. Here, we investigate the role of both the
homeodomain (HD) and the activation domain of Bcd in the anterior repression of its targets.
When a Bcd mutant protein whose HD has been replaced by the Gal4 DNA-binding domain is
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Team Publications
Epigenetic plasticity and polarity of the embryo
expressed in early embryos, a reporter gene driven by Gal4 DNA-binding sites is first
activated in an anterior domain and then repressed from the anterior pole. The downregulation of Bcd-Gal4 activity requires torso function but does not depend on endogenous
bcd activity, indicating that the Bcd protein alone and none of its targets is required to
mediate the effect of torso. Functional analysis of a chimeric protein, whose activation
domain has been replaced by a generic activation domain, indicates that the activation
domain of Bcd is also not specifically required for its down-regulation by Torso. We propose
that Torso does not affect the ability of Bcd to bind DNA, but instead directs modification of
Bcd or of a potential Bcd co-factor, which renders the Bcd protein unable to activate
transcription.
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