Vertebrate nervous system posteriorization: Grading the function of Wnt signaling

Abstract

The establishment of anteroposterior identity in the vertebrate neural plate has been a subject of investigation for decades, but molecular explanations of posteriorization were only revealed beginning in the late 1980s. A model has emerged from several key studies that identifies Wnt signaling as a key posteriorizing agent, which evidence suggests specifies anteroposterior fates in a concentration-dependent manner. In this review, we consider the historical context of posteriorization studies and evaluate models for Wnt-dependent posteriorization. With new information about the mode of delivery of many signaling ligands, we propose alternative scenarios to reconcile the Wnt gradient model with the complex process of gastrulation and potential non-secretory mechanisms of Wnt delivery. Developmental Dynamics 244:507-512, 2015. V C 2014 Wiley Periodicals, Inc.

Models for patterning primary embryonic body axes: The role of space and time

“…This is true for both the patterning along the AP and the DV axes. Several observations suggest that the AP pattern in the brain is under control of a Wnt gradient that is generated at the blastopore/marginal zone [8][9][10]; (reviewed in [11]). The region of forebrain formation has the largest distance to the blastopore and emerges at a low WNT concentration, suggesting that the forebrain is the default state.…”

Temporally coordinated signals progressively pattern the anteroposterior and dorsoventral body axes

“…These four rostral (anterior) to caudal (posterior) subdivisions are the forebrain, midbrain, hindbrain, which is further subdivided into rhombomeres (numbered 1 – 7 from rostral to caudal in the zebrafish), and spinal cord (Fig. 1a) [12]. Although the complete specification of CNS fates extends beyond gastrulation, these subdivisions of the CNS can be used as a reliable readout of AP axial patterning.…”

“…Unlike Wnt signaling, FGF is not sufficient to ectopically induce caudal cell fates in the forebrain [35] or in animal explants [30]. Although this supports a more prominent role for Wnt signaling in specifying the broad subdivisions of the CNS [12], it is notable that FGF is required to generate a permissive environment for the caudalizing activity of Wnt [30]. The complex relationship between FGF and Wnt during neural patterning remains to be fully characterized, but a recent study suggests that Wnt may regulate Sprouty expression, providing a mechanism to coordinate Wnt and FGF signaling [55].…”

“…Specifically, RA induces genes that specify the identity of more caudal hindbrain segments (rhombomeres 4 – 7 in the zebrafish) [97–99] and thus does not play a role in delineating the broad AP subdivisions of the CNS (Fig. 1a) [12,97,100]. …”

Role of cytonemes in Wnt transport

“…Here, Wnt-producing cells are of mesodermal origin and do not intermingle with the ectodermal cells of the neural plate during gastrulation (Keller et al, 2008;Woo, 1997). In summary, the function of Wnt/β-catenin signaling within the neural plate correlates with the formation of a morphogenetic field, and differences in Wnt8a concentrations are responsible for brain subdivisions along the anterio-posterior axis (Bang et al, 1999;Dorsky et al, 2003;Green et al, 2014). Regulation of propagation is fundamental to the formation of a Wnt8a morphogenetic gradient.…”