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

Abstract

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.

Evolution of glial cells: a non-bilaterian perspective

“…In Nematostella , a Gcm ortholog is expressed in a subset of cells during development [ 193 ]. Our recent studies in Nematostella demonstrated that Gcm controls expression of Eaat1 , an astrocyte marker in bilaterians, which is expressed in supposedly neural cells with non-typical morphology [ 219 ]. Future experiments including electrophysiology, loss of function, and reporter lines should clarify genetic and physiological features of these cells.…”