Signaling gradients during paraxial mesoderm development.
The sequential formation of somites along the anterior-posterior axis is under control of multiple signaling gradients involving the Wnt, FGF, and retinoic acid (RA) pathways. These pathways show graded distribution of signaling activity within the paraxial mesoderm of vertebrate embryos. Although Wnt and FGF signaling show highest activity in the posterior, unsegmented paraxial mesoderm (presomitic mesoderm [PSM]), RA signaling establishes a countergradient with the highest activity in the somites. The generation of these graded activities relies both on classical source-sink mechanisms (for RA signaling) and on an RNA decay mechanism (for FGF signaling). Numerous studies reveal the tight interconnection among Wnt, FGF, and RA signaling in controlling paraxial mesoderm differentiation and in defining the somite-forming unit. In particular, the relationship to a molecular oscillator acting in somite precursors in the PSM-called the segmentation clock-has been recently addressed. These studies indicate that high levels of Wnt and FGF signaling are required for the segmentation clock activity. Furthermore, we discuss how these signaling gradients act in a dose-dependent manner in the progenitors of the paraxial mesoderm, partly by regulating cell movements during gastrulation. Finally, links between the process of axial specification of vertebral segments and Hox gene expression are discussed.
Aulehla
Alexander
A
Stowers Institute for Medical Research, Kansas City, Missouri 64110, USA.
Pourquié
Olivier
O
D000818:Animals; D019521:Body Patterning; D004305:Dose-Response Relationship, Drug; D005346:Fibroblast Growth Factors / Q000378:metabolism; D018398:Homeodomain Proteins / Q000378:metabolism; D006801:Humans; D008648:Mesoderm / Q000378:metabolism*; D008954:Models, Biological; D009991:Oscillometry; D015398:Signal Transduction; D019170:Somites; D013997:Time Factors; D014212:Tretinoin / Q000378:metabolism; D051153:Wnt Proteins / Q000378:metabolism
D018398:Homeodomain Proteins; D051153:Wnt Proteins; D014212:Tretinoin; D005346:Fibroblast Growth Factors