Transgenic analysis of a SoxB gene reveals neural progenitor cells in the cnidarian Nematostella vectensis

Abstract

Bilaterian neurogenesis is characterized by the generation of diverse neural cell types from dedicated neural stem/progenitor cells (NPCs). However, the evolutionary origin of NPCs is unclear, as neurogenesis in representatives of the bilaterian sister group, the Cnidaria, occurs via interstitial stem cells that also possess broader, non-neural, developmental potential. We address this question by analysing neurogenesis in an anthozoan cnidarian, Nematostella vectensis. Using a transgenic reporter line, we show that NvSoxB(2) -an orthologue of bilaterian SoxB genes that have conserved roles in neurogenesis -is expressed in a cell population that gives rise to sensory neurons, ganglion neurons and nematocytes: the three primary neural cell types of cnidarians. EdU labelling together with in situ hybridization, and within the NvSoxB(2)::mOrange transgenic line, demonstrates that cells express NvSoxB(2) before mitosis and identifies asymmetric behaviours of sibling cells within NvSoxB (2) + lineages. Morpholino-mediated gene knockdown of NvSoxB (2) blocks the formation of all three neural cell types, thereby identifying NvSoxB(2) as an essential positive regulator of nervous system development. Our results demonstrate that diverse neural cell types derive from an NvSoxB(2)-expressing population of mitotic cells in Nematostella and that SoxB genes are ancient components of a neurogenic program. To our knowledge this is the first description of a lineage-restricted, multipotent cell population outside the Bilateria and we propose that neurogenesis via dedicated, SoxB-expressing NPCs predates the split between cnidarians and bilaterians.

C. elegansSoxB genes are dispensable for embryonic neurogenesis but required for terminal differentiation of specific neuron types

“…SoxB genes have been associated with broad neurogenic functions throughout the animal kingdom, from deuterostomes (chordates, echinoderms, hemichordates) (Burke et al, 2014;Reiprich and Wegner, 2014;Taguchi et al, 2002) and protostomes (Ecdysozoa, Lophotrochozoa) (Kerner et al, 2009;Overton et al, 2002) to even earlier diverging animal lineages such as cnidarians (Richards and Rentzsch, 2014). SoxB proteins are required for neuronal commitment broadly throughout the embryonic nervous system during the earliest stages of development, predominantly in proliferating, undifferentiated precursors (Pevny and Placzek, 2005;Pevny and Nicolis, 2010;Reiprich and Wegner, 2014;Sarkar and Hochedlinger, 2013).…”

Neurogenesis in sea urchin embryos and the diversity of deuterostome neurogenic mechanisms

“…Several studies of neurogenesis indicate that there are common features in components mediating embryonic neurogenesis in a wide range of metazoans (Hartenstein and Stollewerk, 2015). In some metazoans, expression of SoxB2 is a necessary condition for neurogenesis (Richards and Rentzsch, 2014). When we suppressed the expression of SoxB2 with a MASO, there was a reduction in the number of cells expressing SoxC (Fig.…”

“…SoxB2 is an HMG-box-containing transcription factor thought to be important in neuronal differentiation (Richards and Rentzsch, 2014;Taguchi et al, 2002). At hatching, SoxB2 is downregulated at the vegetal pole (Fig.…”

“…There are similarities suggesting homology, but we lack a broad understanding of neural development mechanisms in metazoans. In some organisms neurogenic potential is spread throughout the ectoderm and neural precursors arise and differentiate to form a nerve network (Richards and Rentzsch, 2014;Cunningham and Casey, 2014). In many bilaterians, neurogenesis is restricted to specific domains of ectoderm by early patterning (Bier and De Robertis, 2015).…”

Reconsidering regeneration in metazoans: an evo-devo approach

“…Proliferation of cell populations with a restricted fate seems to be the source of the multiple cell types necessary for the regeneration of the lost structure in some species of anthozoans (Passamaneck and Martindale, 2012). Particularly, a population of lineage-restricted multipotent neural precursors, expressing SoxB, have been identified in Nematostella (Richards and Rentzsch, 2014). Regeneration in cnidarians also occurs via cell transdifferentiation as reported for the regeneration of striated muscle in the hydrozoan jellyfish (Galle et al, 2005), and also in Hydra, where this coexists with stem cell based mechanisms (Siebert et al, 2008).…”