A prime example of this is astrocytes,

which in culture appear more like reactive astrocytes. Therefore, while research in vivo is now widely accepted as essential, the field has been limited by a lack of genetic tools. Fortunately, a new enthusiasm for understanding glial biology is leading to the production of newer tools and experimental animal systems suitable for in vivo studies that can help propel our understanding of basic glial biology. About see more 600 million years ago, there was already great diversity of animal form, as displayed in the fossil record in deposits such as the Burgess Shale in the Canadian Rockies (Figure 2). The first moving multicellular animals, the Cnidarians, began floating about during the Protopaleozoic area. Jellyfish contain only rudimentary nerve nets and very simple light-sensing organelles; glial cells are not obviously present. It may be that nonneuronal support cells from mesodermal Pomalidomide in vivo rather than ectodermal lineages perform very basic support roles for neurons, but this remains to be explored.

The subsequent Paleozoic era is characterized by mass extinctions and intense selective pressure. In animals with slightly more sophisticated neural tissues that include peripheral sensory structures and simple centralized ganglia—such as in C. elegans—glial cells become much more obvious and even in this simple state neuron-glia interactions appear similar to those in higher organisms ( Shaham, 2006 and Stork et al., 2012). Such simple, ectodermally derived nonneuronal support cells may have originated once in a single common ancestor or multiple times in distinct lineages (e.g., through convergent

evolution, atavism, etc.) ( Hartline, 2011). If the former, then studying glial cells in isothipendyl simple model genetic organisms would be expected to bear great fruit in defining ancestral, and presumably the most essential, roles for these cells in neural tissues. If the latter, gaining a deeper understanding of both invertebrate and vertebrate glia would allow for the definition of key hurdles that must have been overcome with respect to neuronal function that allowed for the successful elaboration of more complex nervous systems. Much of the discussion below will rely on the morphology of neuron-glia interactions, because form can be indicative of function, but wherever possible molecular correlates will also be discussed. Upon close inspection, the morphological relationship between glia and neurons in flies and worms makes a strong argument that glia became highly dependent upon neurons very early on in evolution. Worms have a relatively simple nervous system composed of 302 neurons, 50 glial cells of ectodermal origin, and six glial cells of mesodermal origin (Shaham, 2006). All ectodermally derived glia in C. elegans are associated with sensory structures ( Figure 1).