The Questions of Developmental Biology

Eph signaling is thought to mediate cell shape changes, and these could be responsible
for separating the presomitic mesoderm at the EphA4-ephrinB2 border. Thus, ephrin-Eph
signaling may be responsible for converting the prepattern established by the Hairy protein in the
presomitic mesoderm into actual somites.
Epithelialization
Several studies in chicks have shown that the conversion from mesenchymal tissue into
an epithelial block occurs even before each somite splits off. As seen in Figure 14.3, the cells of
the somitomere are randomly organized as a mesenchymal mass, but the synthesis of two
extracellular matrix proteins, fibronectin and N-cadherin, links them into arrays that will form
tight junctions and generate their own basal laminae (Figure 14.5B; Ostrovsky et al. 1984; Lash
and Yamada 1986; Hatta et al. 1987). These extracellular matrix proteins, in turn, may be
regulated by the expression of the Paraxis gene. This gene encodes a transcription factor that is
also expressed at the rostral (anterior) end of the unsegmented mesoderm of mouse embryos, and
which is seen in precisely that region that will form the somite (Figure 14.5C). Injection of
antisense oligonucleotides complementary to the Paraxis message produces defects of the
paraxial mesoderm, and in the somites of Paraxis-deficient mice, no epithelial structures are
formed. These defective somites have segregated from the segmental plate and their cells have
differentiated, but they are completely disorganized (Burgess et al. 1995; Barnes et al. 1997). The
Paraxis protein is therefore an essential part of the conversion from mesenchyme to epithelium
(Burgess et al. 1996; Barnes et al. 1997; Tajbakhsh and Spörle 1998).
Specification and commitment of somitic cell types
Axial specification
Although all the somites look identical, they will form different structures at different
positions along the anterior-posterior axis. For instance, the ribs are derived from somites. The
somites that form the cervical vertebrae of the neck and the lumbar vertebrae of the abdomen are
not capable of forming ribs; ribs are generated only by the somites forming the thoracic vertebrae.
Moreover, the specification of the thoracic vertebrae occurs very early in development. If one
isolates the region of chick segmental plate that will give rise to a thoracic somite, and transplants
this mesoderm into the cervical (neck) region of a younger embryo, the host embryo will develop
ribs in its neck. Those ribs will form only on the side where the thoracic mesoderm has been
transplanted (Figure 14.6; Kieny et al. 1972; Nowicki and Burke 1999). As discussed in Chapter
11 (see Figure 11.41), the somites are specified in this manner according to the Hox genes they
express. Mice that are homozygous for a loss-of-function mutation of Hoxc-8 will convert a
lumbar vertebra into an extra ribbed thoracic vertebra (see Figure 11.39).