Credit:  THE COMPANY OF BIOLOGISTS

During the development of the central nervous system (CNS) or peripheral nervous system (PNS) in Drosophila melanogaster, the neural progenitors (neuroblasts, NB) or the sensory organ precursors, respectively, give rise to lineages of neural and glial cells. Many of the factors that control asymmetric division of the these cells and the development of the neural lineages have been determined. However, previous work has not focused on the mechanisms behind glial cell development. Recent work by Udolph et al. (Development, 128, 1457–1466; 2001) and Van De Bor et al. (Development 128, 1381–1390; 2001) studied the role of Notch — a protein known to be involved in cell communication and with a presumed role in gliogenesis — in this process.

CNS glial cells develop from glioblast or neuroglioblast (NGB) lineages derived from the neuroectoderm or the mesoectoderm, whereas PNS glial cells are derived from mixed lineages. During early lineage development, some NGB lineages bifurcate to produce a glioblast and a neuroblast in an asymmetric manner. Neuroectoderm-derived glioblasts express glial cells missing (gcm), which acts to switch cells between neuronal and glial cell fates. As there are many different glial cell progenitors, Udolph et al. studied the NB1-1A abdominal lineage and showed that it does not bifurcate into more specialized secondary progenitors. Instead, the glial cells share a sibling cell fate relationship with neurons. Without Notch, the glial cells are lost and the neuronal cells are duplicated (see picture). In addition, Notch positively regulates the expression of gcm.

In contrast, Van De Bor et al. studied gliogenesis in the PNS, where gain-of-function Notch mutations also act as a genetic switch between neuronal and glial cell fates. Interestingly, they show that Notch represses neurogenesis or gliogenesis within certain cell types and, in contradiction of the work of Udolph et al., that it represses the expression of gcm.

These studies indicate that Notch regulates by controlling, either positively or negatively, the glial master regulator gcm. Although the precise role of Notch, and its relationship with gcm expression, seems to depend on the neuronal lineage studied, both pieces of work uncover some of the mechanisms used to control the fate of glial cells.