Transformation of a neural activation and patterning model

Abstract

The activation and transformation model of vertebrate nervous system formation posits that neural tissue is initially induced, or activated, with anterior forebrain character. Once established, a subset is then transformed into the more posterior midbrain, hindbrain, and spinal cord by signals emanating from the posterior of the embryo. This has been a predominant model in the field for decades. In the June issue of EMBO Reports, Polevoy and colleagues evaluate the role of signals thought to act as the neural transforming factors during Xenopus development, and find that while these signals are consistent with the activation transformation model during brain patterning, they do not fit the model with respect to spinal cord formation [1]. This work, along with other recent studies on the origin of the spinal cord, necessitates an updated model of vertebrate nervous system formation, where spinal cord induction and patterning is distinct from that of the brain.

Neuromesodermal Lineage Contribution to CNS Development in Invertebrate and Vertebrate Chordates

“…For example, FGF is required for ‘neural induction’ in a- and b-lineages [ 76 ], whereas inhibition of FGF-signaling is required for neural specification in A-lineages ( Figure 5 ; 64-cell stage) [ 88 ]. This is consistent with the hypothesis proposed in vertebrates for distinct molecular mechanisms driving the formation of the anterior and posterior CNS [ 15 , 17 , 18 , 19 , 177 ].…”

“…This anterior character was then ‘transformed’ by posteriorizing signals to generate the entire posterior nervous system (reviewed in [ 15 , 16 ]). The prevailing modern view is that only the anterior nervous system: forebrain, midbrain, hindbrain and anterior part of the spinal cord is induced and transformed from a cellular origin associated with epidermis [ 19 , 20 , 94 , 95 , 96 ]. The posterior part of the nervous system is now thought to arise predominantly from neural-mesoderm precursors (NMps) that generate the paraxial mesoderm and spinal cord [ 15 , 17 , 18 , 20 , 95 , 97 , 98 , 99 , 100 , 101 ].…”

“…This seemed at odds with the observation in ascidian larvae that the anterior and posterior CNS arise from distinct hemispheres of the early embryo, with animal hemisphere-derived anterior neural tissue arising from binary fate choices with epidermis and the vegetal hemisphere-derived posterior CNS arising from binary fate choices with mesoderm. However, in vertebrates, while some posterior neural tissue does form via a process known as “posteriorization”, it has become clear that the posterior-most CNS originates from a distinct ontology to the anterior CNS and is associated with mesoderm fates [ 15 , 17 , 18 , 19 ]. These recent advances may bring the ontologies of the ascidian and vertebrate CNSs closer together than was once believed.…”

Tissue Rotation of the Xenopus Anterior–Posterior Neural Axis Reveals Profound but Transient Plasticity at the Mid-Gastrula Stage

“…Inhibition of the BMP and Wnt signaling pathways were shown to produce initial anterior fates with FGF, Wnt, and retinoic acid acting as posteriorizing, transforming signals [10,68,69]. In order to resolve a significant number of inconsistencies with this initial model, including the presence of ongoing induction of tail CNS from neuromesodermal precursors (NMPs) that never appear to adopt an anterior fate, an updated model has been proposed which argues for two distinct signaling centers and that "primary regionalization" distinguishing the spinal cord from the rest of the CNS is established prior to neural induction [8,9]. While the activation-transformation framework applies well for the hindbrain, midbrain and forebrain, with low BMP and Wnt acting as a transforming factor for hindbrain fates, the spinal cord region is induced and patterned separately, independently, and progressively from a population of NMPs.…”

“…Because of intrinsic interest in the nervous system, as well as the implications for both biomedicine and evolutionary biology, neural development has attracted a significant amount of research effort since the beginning of experimental embryology [1][2][3]. This effort has led to considerable progress in defining both the tissue interactions and the cellular and molecular genetic mechanisms mediating the normal development of the nervous systems [3][4][5][6][7][8][9][10][11][12][13][14][15]. However, the development of functional organ systems not only requires the determinative processes that lead to cell type specificity and appropriate patterning of those cell types, but also the ability to maintain this differentiated, patterned state in the face of ongoing genetic and environmental perturbations that occur throughout embryogenesis [16][17][18].…”