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Somitogénèse et patterning axial
Somitogenesis and axial patterning
Marie Kmita
Genetics and Development
http://www.ircm.qc.ca/LARECHERCHE/axes/neuro/gendev
March 23, 2017
OUTLINE
Part 1: Brief overview on the early steps of embryonic development
Part 2: Building up the body plan: Somitogenesis
Part 3: Patterning the body plan
Gastrulation
Spemann et Mangold, 1924
Spemann et Mangold, 1924
Cell lineage formation from egg to egg cylinder
Rossant, J. et al. Development 2009;136:701-713
The primitive streak
The primitive streak is the structure that:
- establishes bilateral symmetry.
- determine the site of gastrulation.
- initiate the formation of the three germ layers.
The PS is first visible as a thickening of the
epiblast at the posterior region of the embryo.
Thickening due to cell ingression and by the
migration of cells from the lateral region of the
posterior epiblast toward the center. As these
cells enter the PS , the streak elongates toward
the future head region.
The Node, at the anterior end of the PS, is
equivalent of the amphibian organizer.
Cells entering the blastocoel separate in two layers:
- The deep layer joins the hypoblast along the midline. These cells give rise to all endodermal
organs of the embryo as well as most of the extraembryonic membranes.
- the second layer is formed of cells that are located between the endoderm and the epiblast.
These cells give rise to the mesoderm and contribute also to extraembryonic membranes.
The primitive streak is the structure that:
- establishes bilateral symmetry.
- determine the site of gastrulation.
- initiate the formation of the three germ layers.
The PS is first visible as a thickening of the
epiblast at the posterior region of the embryo.
Thickening due to cell ingression and by the
migration of cells from the lateral region of the
posterior epiblast toward the center. As these
cells enter the PS , the streak elongates toward
the future head region.
The Node, at the anterior end of the PS, is
equivalent of the amphibian organizer.
From “Developmental Biology” Scott F Gilbert, sixth edition
Fate of the ingressing cells ?
- Cells that ingress through the node migrate anteriorly and form foregut, head
mesoderm and notochord.
- Cells that ingress through the primitive streak give rise to the majority of endodermal
and mesodermal tissue.
OUTLINE
Part 1: Early steps of embryonic development
Part 2: Building up the body plan: Somitogenesis
Part 3: Patterning the body plan
The vertebrate body plan
Vertebrate body axis is subdivided along the A-P
axis into repeating segments (somites)
The metameric pattern is established early on
during embryonic development (somitogenesis)
Somitogenesis
- Somites are transient structures
- Somites give rise to vertebrae and
their associated muscles and tendons,
dermis of the back and skeletal muscles
of the body wall and limbs.
- During development, somites are formed
sequentially with a precise pace.
- There is a direct correlation between
the time when a given somite forms and
the AP domain of the body plan that
derived from these somitic cells.
Link movie 1
Somites are blocks of cells that form
from paraxial mesoderm and bud off at
the rostral end of the presomitic
mesoderm
The segmentation clock
Cooke and Zeeman proposed in 1976 a theoretical model for
somitogenesis called the ‘clock and wavefront’: cells of the psm possess
an intrinsic oscillator (the clock) which controls their somite forming
ability. This model comprises a second component called the
‘wavefront’, which corresponds to a maturation front.
Hairy1 expression in the PSM
Palmeirim et al., Cell 1997
Palmeirim et al., Cell 1997
Other genes, such as Lfng, Hes7 and Hes1 were identified as cycling genes
These genes are all targets of the Notch signaling and cycle in phase.
A negative feedback loop on Notch signaling is established by Lfng itself.
Notch
+
Notch targets
_
Wnt signaling and the clock
First evidence of the involvement of Wnt signaling in the somitic clock was the
finding that Axin2 expression oscillates in the psm.
Wnt/FGF-based cyclic gene expression is dynamic in the PSM of Hes7−/− embryos.
Ferjentsik et al., PLoS Genet 5(9):
In contrast, members of the Notch pathway require Wnt signaling for oscillation .
Notch and Wnt Signaling are thought to be components of the
oscillator
The segmentation clock
WNT
NOTCH
Internal <clock> of
presomitic mesoderm cells
Complete lack of Notch signaling in the PSM prevents somite formation
Embryo culture with and without Notch
blocking treatment
Ferjentsik et al., PLoS Genet 5(9)
The determination front
A model for somitogenesis
Dubrulle, J. et al. Development 2004;131:5783-5793
The successive steps in somitogenesis
Dubrulle, J. et al. Development 2004;131:5783-5793
Somite number
Somite number
From Gomez & Pourquié, 2009
Summary (part 2)
- Somites are transient structures
- Somites give rise to vertebrae and their associated muscles and tendons, dermis of
the back and skeletal muscles of the body wall and limbs.
- Somitogenesis is a unidirectional process: There is a direct correlation between the
time when a given somite forms and the AP domain of the body plan that derived from
these somitic cells.
- The determination front and molecular clock in the psm drive somite formation
OUTLINE
Part 1: Early steps of embryonic development
Part 2: Building up the body plan: Somitogenesis
Part 3: Patterning the body plan
Homeotic mutations in Drosophila convert one segment into another
The Antennapedia mutation
The Hox genes are conserved from
Flies to Vertebrates
Hox genes encode for transcription
factors characterized by a 60 amino
acids DNA binding domain referred to
as the homeodomain.
Hox genes are organized in clusters: 1
in Drosophila and 4 in Vertebrates,
which are supposed to originate from a
common ancestral cluster through
tandem duplications.
Nested expression of vertebrate Hox genes
X
X
X
control
10Aaccdd
10aaccdd
From Wellick and Capecchi, Science 2003
Relationship between timing of Hox gene activation and
spatial expression pattern along the A-P axis
Spatial and temporal collinearity
From Deschamps and van Nes, 2005
From Deschamps and van Nes, 2005
Patterning outcome of ectopic Hoxa10
©2005 by Cold Spring Harbor Laboratory Press
Carapuço M et al. Genes Dev.2005
Models for Hox-dependent patterning
Hox code
Posterior prevalence
From Kmita & Duboule, Science 2003
Hox, Cdx and the posterior elongation process
Posterior elongation: the role of Cdx genes
Young et al., Developmental Cell 2009
Somitogenesis takes place in Cdx2/4 mutant but there is a
deficiency in PSM cells.
Young et al., Developmental Cell 2009
Posterior elongation: the role of Hox genes
Young et al., Developmental Cell 2009
Posterior elongation: the role of Hox genes
Young et al., Developmental Cell 2009
Molecular network underlying posterior elongation
Young et al., Developmental Cell 2009
The transcriptional control of Hox genes
Morphological evolution
Differences in Hox expression patterns in mouse and chick
Sequential activation of Hox genes
From Deschamps and van Nes, 2005
Models for colinear Hox gene expression
Kmita & Duboule Science 2003
Epigenetic and Hox regulation
Soshnikova and Duboule, Science 2009
Epigenetic and Hox regulation
Soshnikova and Duboule,
Science 2009
Local and long-range regulation of Hox genes
E10.5
E11.5
Spitz et al. Genes Dev. 2001
Expression in distal limbs relies on cis-regulatory sequences located outside the
HoxA cluster
Berlivet et al., Plos Genetics 2013
Models for colinear Hox gene expression
Kmita & Duboule Science 2003
Summary (part 3)
- The architecture of the main body axis, posterior to the head, is established by Hox
genes.
- This process relies on the sequential activation of Hox genes in time, which progresses
from one end of the cluster toward the other end, establishing a collinear relationship
between gene order on the chromosome and the timing of transcriptional activation
(temporal collinearity).
- Body development relies on a posterior elongation process with posterior tissues being
formed last. Thereby, the sequential activation of Hox genes in time leads to the
differential expression along the A-P axis (spatial collinearity).
- The posterior elongation process itself is tightly linked to the function of Hox genes.
- Cell fate is determined by the specific combination of functional Hox proteins, which
varies along the A-P axis.