Regulation of axial stem cells deriving neural and mesodermal tissues during posterior axial elongation

Abstract

The vertebrate body axis elongates by extending the posterior end and generating a variety of somatic cells of the trunk (posterior) tissues. Recent studies have demonstrated that the posterior neural plate and posterior paraxial mesoderm are generated from bipotential stem cells, the axial stem cells, which reside in the caudal lateral epiblast of gastrulating embryos. The fate of axial stem cells, neural or mesodermal lineages, depends on the counteracting transcription factors for respective tissues, Sox2 and Tbx6. Tbx6 represses the Sox2 expression in the axial stem cell-derived mesodermal precursors. In the absence of the Tbx6 gene, Sox2 is ectopically expressed in the mesodermal precursors, causing ectopic neural tube development at the expense of paraxial mesoderm. While producing two somatic lineages, axial stem cells are proliferatively maintained by a process that depends on the Wnt-Brachyury regulatory loop; mutant embryos lacking Wnt3a or Brachyury activity prematurely terminate axis elongation as the result of stem cell exhaustion. Although the axial stem cells serve as a cellular source for the neural and paraxial mesoderm tissues of the trunk, at the craniocervical level these tissues are presumably produced via completely different mechanisms. In this chapter, experimental evidence for axial stem cells and their regulation is summarized.