Download The anterior pattern of the mesoderm is key for the next phase of

10/12/09
The anterior pattern of the mesoderm is key for the next
phase of development: somitogenesis
After mesoderm ingression, medial/lateral patterning establishes distinct
mesodermal domains
somites
somites
notochord
lateral
plate
mesoderm
Distinct mesoderm domains give rise to specific derivatives:
thus, in mesoderm, axes, and then position equals fate
Eomes acts as an early and essential determinant of
extraembryonic and pre-somitic mesoderm
Sequential gene expression determines the
presomitic mesoderm
Mutation of different Tbox genes gives rise to distinct
mesodermal phenotypes
brachyuryTbx6
Tbx6-/- phenotype)
brachyury -/- (“T” phenotype)
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10/12/09
Somitic mesodermal identity is lost in Tbx6 mutant
Additional mutations that compromise somite formation
Include multiple members of the notch signaling pathway
Somitic mesoderm is converted to neural tube-like structures
Notch signaling relies upon cell-cell contact, and is
modulated by several feedback mechanisms
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Feedback regulation of Notch and Notch ligands regulates
neighbor distinctions among cells
Periodicity of somitogenesis, and temporal variation
in expression of notch pathway molecules suggests
that Notch signaling establishes somite boundaries
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10/12/09
Dynamic expression of Notch pathway genes in
“split embryo” prerparations shows oscillatory
behavior of gene expression at transcriptional level
Fix
Culture Fix
Oscllations are intrinsic to somitogenic mesoderm:
they do not rely on surrounding mesodermal, ectodermal,
or endodermal tissues
Culture
unlikely due to cell movement
Notch target genes in presomitic mesoderm cells have
intrinisic oscilliatory expression
Differential adhesion and morphogenesis follow
oscilliatory gene expression and signaling
Mutations in Hes7 (Hes genes are transcriptional effectors of Notch signaling)
disrupt downstream regulation of genes that influence somitogenesis
A model for oscillatory signaling that divides the presomitic mesoderm into
somites in a spatially and temporally ordered manner from anterior to posterior
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10/12/09
1. Anterior expression domain of Mesp2 identifies next
somite’s anterior boundary
2. Activated (NICD) notch and Lfng oscillate in register with
Mesp2
3. Mesp2 regulates Notch activation via Delta regulation
4. Mesp2 protein
oscillates to set
posterior and
anterior domains
of Notch activation
and thus define
somite boundaries
3. Regulation of NICD via Lnfg is disrupted in Mesp2 null
4. Mesp2 and NICD positively regulate Lnfg, and Hes7 provides negative feedback;
the Mesp2 regulation of Lnfg may be direct
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10/12/09
5. A model for the role of Mesp2 in regulating Notch activity via
Dll1, Lnfg and Hes7
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