New roles for Wnt and BMP signaling in neural anteroposterior patterning

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. Synopsis In Xenopus , the caudalizing activities inducing hindbrain (Wnt‐Meis3‐FGF) are uncoupled in time and space from the spinal cord inducing (BMP‐FGF‐Cdx) activities. These observations do not support a model in which a Wnt‐signaling gradient demarcates all anteroposterior neural fates. Inhibition of canonical Wnt‐signaling or its downstream transcription factors eliminates hindbrain, but not spinal cord fates. BMP‐activity promotes posterior spinal cord cell fates in an FGF‐dependent manner, while inhibiting hindbrain fates. A simple high to low Wnt‐gradient cannot explain specification of all cell‐fates along the neural anteroposterior axis. Graphical Abstract Neural patterning in vertebrates is considered to follow a two‐step process with BMP antagonists first inducing anterior neural fate followed by a caudalization step in response to a Wnt morphogen gradient. New data in Xenopus challenges this paradigm.