1. Anatómiai, Szövet- és Fejlődéstani Intézet
Paraxiális mesoderma
és somitogenesis
Dóra Dávid
szomita, somitogenesis, dermatom, myotom, sclerotom
Semmelweis Egyetem
Anatómiai, Szövet- és Fejlődéstani Intézet

2. Classification of the mesoderm
Cells migrated between ecto and endoderm during gastrulation
5 types of mesoderm exist
chorda mesoderm
paraxial mesoderm intermedier mesoderm lateral mesoderm head mesoderm

4. Somitogenesis somites
- Somites are simmetrical, segmental structures appearing in specific timeframes lateral to the neural tube
- They originate from paraxial mesoderm
-During their differentiation their progenitor cell will form the:
vertebrae, ribs, intervertebral discs
dermis, hipodermis
back, thoracic, abdominal, limb skeletal muscles

5. Direction of somitogenesis
cranial
Ephrin and its receptor constitute a possible cut site for somite formation
Direction of somitogenesis
caudal
EphA4
Somitogenesis: repeating sequence of similar morfogenetic events
Cranio-caudal directed process

6. Paraxial mesoderm Neural tube somite Paraxial mesoderm
Humán embrióban somita fejlődik ki
Paraxial mesoderm
Neural tube
somite
Paraxial
mesoderm

7. Formation of somites
Shape: like a ball, covered by epithelial cells, inside mesenchyme
One pair of somites form during a species specific time-frame (in chick embryo it is 90 minutes)
They are identical in size .

8. Clock and Wavefront model
Somites form during preset time-frame, but the 7 cranial somitomer never transform into somites  origin of head mesoderm, and of skeletal muscles of head
The time-adjusted cyclical process is depicted by the „Clock and Wavefront” model
Presence of oscillatorically expressing genes in paraxial mesoderm → expression interval of these genes are identical with the time frame of somite formation
FGF8 (produced by Hensen’s node and tail bud) and retinoic acid (produced by already formed somites) establish an oppository gradient in the cranio-caudal axis of the embryo
FGF8 and retinoic acid „extinguishing” each other time the expression of „oscillatory genes”

9. Somitogenesis

10. Delta-Notch are expressed at presumptive boundaries
Ectoderm induction with Wnt-6 will induce the paraxis gene, thus expression changes the mesenchymal somitomer into a epithelial somite
DevBio9e-Fig R.jpg

11. Somites further differenciate after their formation:
Sclerotome
Syndetome
Dermomyotom

12. Sclerotome:
Ventromedial cell group of somites. During multiple mitosis they migrate around the developing neural tube and notochord due to the effect of Shh and noggin, produced by the latters  Expression of Pax-1 and Pax-9 begins  secondary mesenchyme formation and production of cartilage-specific ECM molecules.
Dermomyotome:
Effect of ectodermal Wnt secretion differentiate it to two parts: dermatome (close to the ectoderm). Progenitors of dermotome (together with progenitors from the lateral mesoderm) together will establish the layers of dermis and hypodermis
The part closer to the neural tube of the dermomyotome will be the myotome. Later it contributes to the development of skeletal muscles of the body wall, limbs and back. Cells of the dermomyotom express Pax-3 and Pax-7
Syndetome:
Layer between the sclerotome and dermomyotome. Its cells will differentiate to the precursors of tendocytes

13. Differentiation of somites
noggin

14. Sclerotome determination
Shh signaling from notochord/floor plate
Inducing Pax1 expression

15. Ventral sclerotome: corpus vertebrae, discus intervertebralis
Lateral sclerotome: distal ribs
Medial sclerotome (not shown): meninges and vessels (meningotome)
Arthrotome: discus intervertebralis, proximal ribs
Dorsal sclerotome: dorsal part of arcus vertebrae, processus spinosus
Central sclerotome: ventral part of arcus vertebrae, processus transversus

16. Sclerotomes will split to a cranial and caudal segment further
The caudal segment is more compacted, the cranial is more loosened
Two neighbouring sclerotome’s caudal and cranial segments will form a vertebra
Motoneurons’ axons from the neural tube just can pass through the loosened cranial segment

17. Differentiation of sclerotome:
Formation of vertebrae
caudal
cranial

18. Somites and their sclerotomes are identical but vertebrae are different...
Explanation is the differential expression of HOX genes and the so called HOX-code

19. epithelio-mesenchymal transmission
dermamyotom
Dermatom
ectoderm
epidermis
dermis
dermatome
hypo-dermis
epithelio-mesenchymal transmission
Neural tube
neurotropin 3 (NT-3)

20. dermamyotome Myotom Body wall Tongue muscles Back muscles Limb msucles
Progenitors of epimere will form: m. erector spinae and transversospinal muscles (epaxial muscles)
Progenitors of hypomere will form: intercostal muscles, m. obliquus externus, m. obliquus internus, m. transversus abdominis and limb muscles
Noggin signal from notochord inhibits ectodermal BMP-4, instead of Pax-3 and Pax-7 myogenic factors starts to express, like MyoD or Myf5

21. Migration of myoblasts
limb bud
Migrating myoblasts
BMP-4 from the lateral mesoderm extinguishes the myogenic effect,
And cells start to express Pax-3 
C-met: tirosine kinase receptor protein appears on the surface of myoblasts, to what HGF (hepatocyte growth factor) binds as a ligand  expressed by the limb bud’s mesenchymal cells

22. Trunk muscles at the level of limb buds
epaxial myotome
Autochton back musculature
no hypaxial myotome
Pax-3, HGF/SF, c-met
Myogenic cells for limb muscles

23. Abdominal and intercostal muscles
Between lim buds
Surface ectodern
dermatome
epaxial myotome
autochton hátizomzat
sclerotome
hypaxial myotome
Abdominal and intercostal muscles
Wolffian duct

24. CSIR
Chicken limb bud
quail
chick
Quail derived muscle

25. Development of tendons: expression of sclereaxis gene
devbio8e-fig jpg

26. DevBio9e-Fig jpg