Evolution of glial cells: a non-bilaterian perspective.

Nervous systems of bilaterian animals generally consist of two cell types: neurons and glial cells. Despite accumulating data about the many important functions glial cells serve in bilaterian nervous systems, the evolutionary origin of this abundant cell type remains unclear. Current hypotheses regarding glial evolution are mostly based on data from model bilaterians. Non-bilaterian animals have been largely overlooked in glial studies and have been subjected only to morphological analysis. Here, we provide a comprehensive overview of conservation of the bilateral gliogenic genetic repertoire of non-bilaterian phyla (Cnidaria, Placozoa, Ctenophora, and Porifera). We overview molecular and functional features of bilaterian glial cell types and discuss their possible evolutionary history. We then examine which glial features are present in non-bilaterians. Of these, cnidarians show the highest degree of gliogenic program conservation and may therefore be crucial to answer questions about glial evolution.

Analysis of cnidarian Gcm suggests a neuronal origin of glial EAAT1 function.

In bilaterian central nervous systems, coordination of neurotransmission by glial cells enables highly sophisticated neural functions. The diversity of transcription factors (TFs) involved in gliogenesis suggests multiple evolutionary origins of various glial cell types of bilaterians. Many of these TFs including the glial cells missing (Gcm) are also present in genomes of Cnidaria, the closest outgroup to Bilateria, but their function remains to be elucidated. In this study, we analyzed the function of Gcm, a multifunctional TF involved in development of glial and non-glial cell types, in the sea 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 cells with flat cell bodies and no clear processes. Together with the finding of unique morphological features of NvEAAT1-functioning cells, these data suggest that extracellular glutamate metabolism, one of major glial functions, is deployed downstream of Gcm in specific neural cell types in Cnidaria.