Figure 6. An integrated view of somite morphogenesis.

a. Multiple inputs are integrated to generate somites with regular morphology. The clock and wavefront system periodically lays down a prepattern of gene expression. The size of the prepattern determines the number of cells that undergo differentiation altogether in this somitic cycle. In the region of the prepattern, organized signaling and physical cascades are initiated. They feed into the intrinsic ability of somitic cells to form epithelial rosettes, whose shapes are further finetuned by mechanical cues.

b. Understanding major inputs affected may be helpful to decipher somite shapes in various contexts. Matrigel, Retinoic acid, and the transcription factor Paraxis may elevate the intrinsic ability to form epithelial rosettes.

c. The irregular somite shapes often observed in stem cell-derived organoids result from futile mechanical tuning in contrast to embryos.

d. When the clock and wavefront system is disrupted as in Hes7-null mice, regular prepatterns that organize cell differentiation and signaling cascades cannot be established. Hence, somites can only be irregularly assembled reflecting the intrinsic machinery of rosette formation.

e. The phenomenon that somite size scales with PSM length might be achieved through the modulation of prepattern size by the clock and wavefront system. The prepattern size determines the number of cells that will be incorporated into a forming somite and thus its eventual size.