1. Notch target genes in presomitic mesoderm cells have
intrinisic oscilliatory expression

2. disrupt downstream regulation of genes that influence somitogenesis
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
somite’s 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. the Mesp2 regulation of Lnfg may be direct
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
N-cadherin
N-cadherin
patterning
disrupted locally
ectopic
notochord

15. Somitic patterning facilitates differentiation
of all musculo-skeletal derivatives
scleraxis

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