Tales of Tails (and Trunks): Forming the Posterior Body in Vertebrate Embryos

Abstract

A major question in developmental biology is how the early embryonic axes are established. Recent studies using different model organisms and mammalian in vitro systems have revealed the surprising result that most of the early posterior embryonic body forms from a Wnt-regulated bipotential neuromesodermal progenitor population that escapes early germ layer patterning. Part of the regulatory network that drives the maintenance and differentiation of these progenitors has recently been determined, but much remains to be discovered. This review discusses some of the common features present in all vertebrates, as well as unique aspects that different species utilize to establish their anterior-posterior (A-P) axis.

Keywords: Neuromesodermal cells; Posterior body; Progenitor cells; Tail; Vertebrate development; Wnt signaling.

Figure 1. Morphological features of the vertebrate posterior body

(A) A generic cross section through the post-anal region of a vertebrate embryo. In the pre-anal region, the pronephric tubules and gut tube would also be present. (B) The posterior of the embryo is divided into pre-anal trunk and post-anal tail. Shown is a zebrafish embryo but the same division applies to all vertebrates.

Figure 2. Maintenance of the neuromesodermal progenitors

Lineage labeling studies in the mouse show that while many germ layer decisions are made early, a neuromesodermal progenitor population continues to produce both neural and mesodermal cells during the somitogenesis stages (Tzouanacou et al., 2009). The times at which the gastrula stage fate decisions are made is approximate.

Figure 3. Model for regulation of mesoderm formation in zebrafish

Sox2-expressing NMP cells are in a zone of moderate Wnt signaling (light orange) that maintains Brachyury. As cells leave this region, if they are not exposed to continued Wnt signaling, they express Sox2 but not Brachyury and become neural. Instead, if they are exposed to high levels of Wnt (dark orange) they express Tbx16, which represses Sox2. Tbx16 also represses Wnts so as cells continue to move anteriorly (left side), they shut off Brachyury and turn on mesodermal differentiation genes, thus locking in the mesodermal choice.

Figure 4. Comparison of the regulatory logic of fish and mouse posterior cell fate choices

A schematic showing the regulatory relationships among signaling and transcription factors discussed in this review. Tbx6 is shown here to cause repressive effects indirectly, but as with Tbx16, it may turn out to be able to directly repress target genes. Fgf is omitted for simplicity.

Figure 5. Model for termination of axis extension in chick

During somitogenesis, the progenitor domain excludes RA. Near the end of somitogenesis, the most posterior Hox genes, possibly together with other molecular changes, causes RA to expand posteriorly, thus inhibiting the progenitor cell fate.