An Early Role for Wnt Signaling in Specifying Neural Patterns of Cdx and Hox Gene Expression and Motor Neuron Subtype Identity

Abstract

The link between extrinsic signaling, progenitor cell specification and neuronal subtype identity is central to the developmental organization of the vertebrate central nervous system. In the hindbrain and spinal cord, distinctions in the rostrocaudal identity of progenitor cells are associated with the generation of different motor neuron subtypes. Two fundamental classes of motor neurons, those with dorsal (dMN) and ventral (vMN) exit points, are generated over largely non-overlapping rostrocaudal domains of the caudal neural tube. Cdx and Hox genes are important determinants of the rostrocaudal identity of neural progenitor cells, but the link between early patterning signals, neural Cdx and Hox gene expression, and the generation of dMN and vMN subtypes, is unclear. Using an in vitro assay of neural differentiation, we provide evidence that an early Wnt-based program is required to interact with a later retinoic acid- and fibroblast growth factor–mediated mechanism to generate a pattern of Cdx and Hox profiles characteristic of hindbrain and spinal cord progenitor cells that prefigure the generation of vMNs and dMNs.

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.…”

Two Hoxc6 transcripts are differentially expressed and regulate primary neurogenesis in Xenopus laevis

“…This confirmed the role of Hox genes in defining axial identities (McGinnis and Krumlauf, 1992). Furthermore, Hox genes were also connected to the patterning of the neural tube and its subtypes of neurons (Dasen et al, 2003;Song and Pfaff, 2005;Nordström et al, 2006;di San-guinetto et al, 2008). Hox gene expression has been correlated to the identities of motor neurons along the spinal cord (Shah et al, 2004).…”

Retinoid signalling is required for information transfer from mesoderm to neuroectoderm during gastrulation

“…However, experiments in avian embryos have suggested that the later somitic mesoderm can also signal to impart pattern onto the hindbrain in a retinoid-dependent way (Itasaki et al, 1997;Gould et al, 1998). Moreover, regionalisation of the avian posterior hindbrain seems to coincide with the beginning of somitogenesis (Nordström et al, 2006). This timing difference could be due to distinctive characteristics of each species: in Xenopus the mesoderm migrates as a sheet (involution) which may allow for an early and robust source of signal to pattern the overlying neuroectoderm during gastrulation, whereas the cellby-cell mode of mesoderm migration in the avian embryo is less favourable for local delivery of the morphogen (RA).…”