New roles for Wnt and BMP signaling in neural anteroposterior patterning

Abstract

During amphibian development, neural patterning occurs via a two‐step process. Spemann's organizer secretes BMP antagonists that induce anterior neural tissue. A subsequent caudalizing step re‐specifies anterior fated cells to posterior fates such as hindbrain and spinal cord. The neural patterning paradigm suggests that a canonical Wnt‐signaling gradient acts along the anteroposterior axis to pattern the nervous system. Wnt activity is highest in the posterior, inducing spinal cord, at intermediate levels in the trunk, inducing hindbrain, and is lowest in anterior fated forebrain, while BMP‐antagonist levels are constant along the axis. Our results in Xenopus laevis challenge this paradigm. We find that inhibition of canonical Wnt signaling or its downstream transcription factors eliminates hindbrain, but not spinal cord fates, an observation not compatible with a simple high‐to‐low Wnt gradient specifying all fates along the neural anteroposterior axis. Additionally, we find that BMP activity promotes posterior spinal cord cell fate formation in an FGF‐dependent manner, while inhibiting hindbrain fates. These results suggest a need to re‐evaluate the paradigms of neural anteroposterior pattern formation during vertebrate development.

Fgf/Ets signalling inXenopusectoderm initiates neural induction and patterning in an autonomous and paracrine manners

“…S2E, F, G). This characteristic of anterior neural genes being suppressed by a higher dose of Fgfs may explain why a high level of Fgf signalling notably suppressed anterior development, as previously reported (Cox and Hemmati-Brivanlou, 1995; Lamb and Harland, 1995; Pownall et al, 1996; Polevoy et al, 2019).…”

Modeling Bainbridge-Ropers Syndrome in Xenopus laevis Embryos

“…These observations also suggest that ASXL3 may function in the earliest network of genes regulating the specification of posteriortrunk neural tissue such as hindbrain, primary neurons and neural crest. This phenotype is quite similar to the knockdown phenotype for the Meis3 homeodomain protein (Dibner et al, 2001;Gutkovich et al, 2010) or embryos disrupted for early Wntsignaling, where hindbrain, neural crest, and primary neuron cell fates are lost, but the spinal cord forms quite normally Polevoy et al, 2019).…”

Transformation of a neural activation and patterning model

“…The manuscript by Polevoy et al in this issue revisits some of the signaling factors that have been implicated in the activation and transformation model, including BMP, FGF, and canonical Wnt signaling . They identify new roles for these factors that also run contrary to the activation and transformation model.…”

“…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.…”