Nodal–Activin pathway is a conserved neural induction signal in chordates

Abstract

Neural induction is the process through which pluripotent cells are committed to a neural fate. This first step of Central Nervous System formation is triggered by the "Spemann organizer" in amphibians and by homologous embryonic regions in other vertebrates. Studies in classical vertebrate models have produced contrasting views about the molecular nature of neural inducers and no unifying scheme could be drawn. Moreover, how this process evolved in the chordate lineage remains an unresolved issue. In this work, by using graft and micromanipulation experiments, we definitively establish that the dorsal blastopore lip of the cephalochordate amphioxus is homologous to the vertebrate organizer and is able to trigger the formation of neural tissues in a host embryo. In addition, we demonstrate that Nodal/Activin is the main signal eliciting neural induction in amphioxus, and that it also functions as a bona fide neural inducer in the classical vertebrate model Xenopus. Altogether, our results allow us to propose that Nodal/Activin was a major player of neural induction in the ancestor of chordates. This study further reveals the diversity of neural inducers deployed during chordate evolution and advocates against a universally conserved molecular explanation for this process.

Dorsal-ventral patterning in amphioxus: current understanding, unresolved issues, and future directions

“…Although at the onset of gastrulation amphioxus Chordin is indeed expressed in both dorsal mesoderm and ectoderm, this ectodermal Chordinexpressing region most likely contributes to the future posterior and trunk CNS due to the lack of extensive involution of tissues around the blastopore during amphioxus gastrulation (Zhang et al, 1997), which is in contrast to the Xenopus BCNE center that would eventually involute and contribute to most of the anterior CNS . In addition, a recent study showed that animal cap explants from early gastrula (G1) stage amphioxus embryos were not able to differentiate into CNS tissues autonomously (Le Petillon et al, 2017), suggesting that neural induction probably begins during gastrulation in the amphioxus embryos.…”

“…Nodal signaling has been shown to play a major role in the DV axis determination in the amphioxus embryo (Le Petillon et al, 2017;Morov et al, 2016;Onai et al, 2010). At the start of gastrulation, both Nodal and Lefty are expressed in the dorsal region ( Fig.…”

“…Stabilized b-catenin is accumulated in the cytoplasm and eventually translocated into the nucleus, where it acts as a transcriptional coactivator with transcription factors that belong to the TCF/LEF family (Hikasa and Sokol, 2013 an early branch of the chordate group, and more importantly, both classical grafting experiments and recent molecular analyses have demonstrated that the dorsal blastopore lip of the amphioxus gastrula has the ability to induce a partial (Tung et al, 1962) or complete (Le Petillon et al, 2017) secondary axis and expresses an array of regulatory genes similar to that expressed by the vertebrate dorsal organizer (Tung et al, 1962;Yu et al, 2007). Furthermore, recent studies have shown that the Nodal and Bmp signaling pathways appear to play conserved roles in amphioxus DV patterning (Kozmikova et al, 2013;Le Petillon et al, 2017;Onai et al, 2010), although the role of Wnt/b-catenin in amphioxus early axial patterning is less clear. In this review, we aim to summarize the current state of research on the formation of the amphioxus organizer and DV axis patterning from the start of development through the early gastrula stage.…”

Novel polyclonal antibodies as a useful tool for expression studies in amphioxus embryos

“…On the other hand, monoclonal antibodies are costly and are not within the reach of a typical lab working in the area of evolutionary developmental biology. Commercially available antibodies produced for vertebrate research can in principle be used if directed against a highly conserved epitope shared by vertebrate and amphioxus protein.Currently, only antibodies against acetylated tubulin are routinely used (Le Petillon et al, 2017;Lu et al, 2012;Soukup et al, 2015;Vopalensky et al, 2012). A fairly small number of antibodies (all polyclonal) has so far been generated that specifically recognize amphioxus proteins in developing embryos (Vopalensky et al, 2012;Wu et al, 2011).…”

“…Currently, only antibodies against acetylated tubulin are routinely used (Le Petillon et al, 2017;Lu et al, 2012;Soukup et al, 2015;Vopalensky et al, 2012). A fairly small number of antibodies (all polyclonal) has so far been generated that specifically recognize amphioxus proteins in developing embryos (Vopalensky et al, 2012;Wu et al, 2011).…”