Chapter 7 Establishment of Hox Vertebral Identities in the Embryonic Spine Precursors

Abstract

Summary The vertebrate spine exhibits two striking characteristics. The first one is the periodic arrangement of its elements – the vertebrae – along the antero-posterior axis. This segmented organization is the result of somitogenesis, which takes place during organogenesis. The segmentation machinery involves a molecular oscillator – the segmentation clock – which delivers a periodic signal controlling somite production. During embryonic axis elongation, this signal is displaced posteriorly by a system of traveling signaling gradients – the wavefront – which depends on the Wnt, FGF and retinoic acid pathways. The other characteristic feature of the spine is the subdivision of groups of vertebrae into anatomical domains, such as the cervical, thoracic, lumbar, sacral and caudal regions. This axial regionalization is controlled by a set of transcription factors called Hox genes. Hox genes exhibit nested expression domains in the somites which reflect their linear arrangement along the chromosomes– a property termed colinearity. The colinear disposition of Hox genes expression domains provides a blueprint for the regionalization of the future vertebral territories of the spine. In amniotes, Hox genes are activated in the somite precursors of the epiblast in a temporal colinear sequence and they were proposed to control their progressive ingression into the nascent paraxial mesoderm. Consequently, the positioning of the expression domains of Hox genes along the antero-posterior axis is largely controlled by the timing of Hox activation during gastrulation. Positioning of the somitic Hox domains is subsequently refined through a cross talk with the segmentation machinery in the presomitic mesoderm. In this review, we focus on our current understanding of the embryonic mechanisms that establish vertebral identities during vertebrate development.

Predicting embryonic patterning using mutual entropy fitness and in silico evolution

“…We use the fitness function to evolve a patterning network in two cases that broadly exemplify what is seen in AP patterning in arthropods and vertebrates: (1) a static morphogen gradient that disappears before the fitness is measured; and (2) a sliding, or translating, morphogen, motivated by somitogenesis and Hox patterning (Francois et al, 2007;Dubrulle et al, 2001;Iimura et al, 2009).…”

“…5E). If we smooth our sliding input step to make the transition from off to on gradual, then our model can readily capture another feature of Hox patterning termed 'anterior spreading' (Kmita and Duboule, 2003;Iimura et al, 2009). It is most obvious in chick,…”

“…We use this fitness to evolve networks to pattern the AP axis under general conditions that span those observed in arthropods and vertebrates: (1) a global morphogen gradient that disappears before the end of embryogenesis; and (2) a sliding morphogen that models patterning during growth (Francois et al, 2007;Peel et al, 2005;Iimura et al, 2009). Position is defined by exposure to the morphogen, but the networks are otherwise cellautonomous.…”

On growth and form: a Cartesian coordinate system of Wnt and BMP signaling specifies bilaterian body axes

“…Thus, just as for Hox genes, what is evolutionarily conserved is the involvement of Wnts in the patterning of the long axis per se, rather than a role in gastrulation, germ layer specification, specific cell-type or organ specification or a particular differentiation process (Erwin and Davidson, 2002). Incidentally, Wnt signaling might regulate Hox gene expression in AP axis formation (Nordstrom et al, 2006;Pilon et al, 2006;Iimura et al, 2009), and the functional coupling of these two mechanisms in primary axis formation might also represent an ancient feature. Taken together, there is a strong case for Wnt signaling in primary axis patterning being an ancestral property that is already found in Urbilateria.…”

Statistical analysis of associated vertebra and costal anomalies in spina bifida patients

“…Somites are paired structures localized on both sides of the embryonic midline that are constructed from mesoderm-derived epithelial blocks. They take their final shape following segmentation of the presomitic mesoderm (2,4,9,25,27). Vertebrae, ribs, intervertebral discs, related skeletal muscles, and connective tissue originate from these somites.…”