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The making of the somite: molecular events in vertebrate segmentation

Nature Reviews Genetics volume 2, pages 835–845 (2001)Cite this article

Key Points

  • During somitogenesis, presomitic mesoderm (PSM) can be divided into at least two distinct regions: region I (posterior PSM) and region II (anterior PSM), which correspond to the two distinct cellular states, state I and state II.

  • No signs of segment specification can be detected at a molecular or cellular level in region I, but PSM cells acquire rostrocaudal polarity and become competent to segment once they have reached region II.

  • Cyclical gene expression that reflects an underlying segmentation clock is translated into Notch activity that keeps the oscillations of neighbouring PSM cells synchronized in region I.

  • Expression of delta-like 1 (Dll1) in region II, which is regulated by mesoderm posterior 2 (Mesp2) through the Notch signalling pathway, determines the rostrocaudal polarity of somites.

  • Notch signalling can be either presenilin 1 (Psen1) dependent or independent; the former is involved in inducing Dll1 expression and the latter in inhibiting Dll1 expression. Mesp2 might stimulate the inhibitory pathway and suppress the induction pathway.

  • The transition from state I to state II is controlled by the level of fibroblast growth factor (Fgf) signalling. A high level of Fgf activation in the posterior PSM maintains PSM cells in an immature state, whereas low Fgf levels accelerate the maturation process of PSM cells in the anterior PSM.

  • Because the Fgf activation domain retreats as somitogenesis proceeds, the wavefront, which is the interphase between region I and region II, gradually moves back. So, periodic interactions between the wavefront and the oscillation wave create a regularly spaced somite border.

Abstract

The reiterated structures of the vertebrate axial skeleton, spinal nervous system and body muscle are based on the metameric structure of somites, which are formed in a dynamic morphogenetic process. Somite segmentation requires the activity of a biochemical oscillator known as the somite-segmentation clock. Although the molecular identity of the clock remains unknown, genetic and experimental evidence has accumulated that indicates how the periodicity of somite formation is generated, how the positions of segment borders are determined, and how the rostrocaudal polarity within somite primordia is generated.

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Figure 1: Somitogenesis in mouse and zebrafish embryos.
Figure 2: Components of the Notch signalling pathway that might be involved in somitogenesis.
Figure 3: Expression pattern of segmentation genes in the presomitic mesoderm.
Figure 4: Genetic evidence for the requirement of Mesp2 in establishing rostrocaudal polarity.
Figure 5: Manipulation of an Fgf signal alters somite size in zebrafish.
Figure 6: A model of somite segmentation.

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Author information

Authors and Affiliations

  1. Division of Mammalian Development, National Institute of Genetics, Yata 1111, Mishima, 411-8540, Japan

    Yumiko Saga

  2. Division of Early Embryogenesis, National Institute of Genetics, Yata 1111, Mishima, 411-8540, Japan

    Hiroyuki Takeda

  3. Department of Biological Sciences, Graduate School of Science, University of Tokyo, Hongo 7-3-1, Bunkyo-ku, 113-0033, Tokyo, Japan

    Hiroyuki Takeda

Authors
  1. Yumiko Saga
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  2. Hiroyuki Takeda
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Corresponding author

Correspondence to Yumiko Saga.

Related links

Related links

DATABASES

FlyBase 

Delta

Fringe

Furin

Kuzbanian

Notch

Serrate 

LocusLink 

brachyury

cerberus 1

c-hairy1

Delta

DeltaC

deltaD

Delta2

Dll1

Dll3

engrailed

FGF8

fgf8

Fgfr1

her1

Hes1

Hey

Lfng

LFNG

Meso1

mesogenin

mespb

Mesp2

Notch

Notch1

Notch2

PAPC

Psen1

Rbpsuh

sonic hedgehog

Thylacine1

Uncx4.1

Wnt

Glossary

PARAXIAL MESODERM

A subpopulation of mesoderm that lies on both sides of the neural tube, which gives rise to somites.

CEPHALOCHORDATE

A subphylum of chordates that includes the amphioxus Branchiostoma, which has a notochord, dorsal nervous system and segmented trunk, but lacks characters such as complex paired sensory organs and a true brain.

PRESOMITIC MESODERM

Precursor unsegmented mesoderm, which generates somites on segmentation.

CYCLING GENE

A gene, the expression of which oscillates rostrocaudally in the presomitic mesoderm.

ROSTROCAUDAL POLARITY

The difference between the rostral (anterior) and caudal (posterior) halves of a somite that underlies a difference in future developmental fates.

SEGMENT-POLARITY GENE

A gene originally identified in Drosophila early development, the expression of which divides the embryo into units that are 14 segments wide.

SCLEROTOME

Mesenchymal cell mass located in the medial region of a somite, from which the axial skeleton derives

PRIMITIVE STREAK

A longitudinal cleft formed on the surface of the amniote early embryo by a convergence of cells. At the onset of gastrulation, epiblast cells migrate towards and into the streak, and in so doing acquire mesodermal cell fate.

TAILBUD

The caudal end of the tail region at which gastrulation continues to generate precursors for the paraxial mesoderm and the neural tube.

EPITHELIAL SOMITE

Spherical epithelial structure made up of epithelial cells that differentiate from mesenchymal cells on segmentation.

AMNIOTE

Animal, such as reptile, bird or mammal, whose eggs contain an amnion — a membrane that surrounds the embryo and helps retain fluids.

SURFACE ECTODERM

The outermost germ layer of the embryo that develops during gastrulation. Also the cell layer that covers the paraxial mesoderm, from which several diffusible factors are secreted that induce somitic cells to take on the dermomyotome fate.

DERMOMYOTOME

Epithelial cell layer in the dorsolateral region of the somite that faces the ectoderm and further differentiates into the most dorsal dermatome, which later differentiates into dermis and myotome — future skeletal muscles.

NEURONAL HYPERPLASIA

Excessive formation of neuronal tissues due to transdifferentiation as a result of defects in Notch signalling.

HOMOTYPIC INTERACTION

Protein interaction between molecules of the same type.

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Saga, Y., Takeda, H. The making of the somite: molecular events in vertebrate segmentation. Nat Rev Genet 2, 835–845 (2001). https://doi.org/10.1038/35098552

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