A genome-wide survey of cnidarian Gcm-dependent genes suggests a neuronal origin of glial function

Abstract

In bilaterian central nervous systems, coordination of neurotransmission by glial cells enables highly sophisticated neural functions. However, it is unclear when glial cells became functional in metazoan evolution. Because cnidarians are the closest outgroup to the Bilateria, we analyzed the function of glial cells missing (Gcm), the core bilaterian gliogenic transcription factor (TF), in the anemone, Nematostella vectensis. siRNA-mediated knockdown of Nematostella Gcm altered expression of cell adhesion proteins, glutamate and GABA transporters, ion channels, metabolic enzymes, and zinc finger and Ets-related TFs. NvGcm and mRNAs of downstream genes are expressed in broad neural cell clusters. However, immunostaining of a NvGcm target protein, the glutamate transporter, NvEAAT1, visualized a novel class of neural cells with flat cell bodies and no clear neurite processes. Our study showed that Gcm drives expression of a glial gene set in N. vectensis, indicating that the evolutionarily conserved gliogenic program functions in cnidarian neurons. Together with the finding of unique morphological features of NvEAAT1-functioning cells, these data suggest that major glial functions, including extracellular glutamate metabolism, were already deployed downstream of Gcm in pre-bilaterian nervous systems.