Notch target genes in presomitic mesoderm cells have - PowerPoint PPT Presentation

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Notch target genes in presomitic mesoderm cells have

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... distinction of sclerotome and derma-myotome depends upon notochord-derived signals N-cadherin ectopic notochord N-cadherin patterning disrupted locally ... – PowerPoint PPT presentation

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Title: Notch target genes in presomitic mesoderm cells have


1
Notch target genes in presomitic mesoderm cells
have intrinisic oscilliatory expression
2
Mutations in Hes7 (Hes genes are transcriptional
effectors of Notch signaling) disrupt downstream
regulation of genes that influence somitogenesis
3
Differential adhesion and morphogenesis follow
oscilliatory gene expression and signaling
4
A model for oscillatory signaling that divides
the presomitic mesoderm into somites in a
spatially and temporally ordered manner from
anterior to posterior
5
1. Anterior expression domain of Mesp2 identifies
next somites anterior boundary
6
2. Activated (NICD) notch and Lfng oscillate in
register with Mesp2
7
3. Mesp2 regulates Notch activation via Delta
regulation
8
4. Mesp2 protein oscillates to set posterior
and anterior domains of Notch activation and thus
define somite boundaries
9
3. Regulation of NICD via Lnfg is disrupted in
Mesp2 null
10
4. Mesp2 and NICD positively regulate Lnfg, and
Hes7 provides negative feedback the Mesp2
regulation of Lnfg may be direct
11
5. A model for the role of Mesp2 in regulating
Notch activity via Dll1, Lnfg and Hes7
12
Somites are patterned locally to generate axial
skeleton and muscalature
13
Somitic patterning depends upon signals from
an increasingly complex set of local organizers
and these signals in turn activate
locally distinct transcriptional programs
14
Somitic distinction of sclerotome and
derma-myotome depends upon notochord-derived
signals
15
Somitic patterning facilitates differentiation of
all musculo-skeletal derivatives
16
Myogenesis relies upon activation of distinct
transcriptional program in myotome-derived
myogenic precursors
17
Skeletogenesis requires cell migration from
sclerotome followed by aggregation and local
morphogenesis
18
Distinct network of local signals and
transcriptional regulators defines
skeletogenesis and differenttiates ti from
myogenesis
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