6-4T neuroglioblast in anaphase showing accumulation of glide/gcm RNA (red) at the medio-basal anterior side. α-Tubulin (green), chromatin (blue). Image courtesy of Angela Giangrande, Institut de Génétique et Biologie Moléculaire et Cellulaire, Strasbourg, France. Animated online (please note that this movie make take a few moments to download)

The developing Drosophila central nervous system (CNS) contains at least two types of neural precursor cell — neuroblasts, which generate neurons only, and neuroglioblasts, which give rise to both neurons and glia. The generation of glia depends on the transcription factor Glide/gcm (Glial cell deficient/glial cell missing). Like many neuroblasts, neuroglioblasts divide asymmetrically and their progeny become specified by cell fate determinants that segregate into one or other of the daughter cells. As reported in Developmental Biology, Ragone et al. have examined the segregation of glide/gcm RNA during neuroglioblast division and, in the process, have uncovered some distinctive features of the mode of asymmetric division in these cells.

The authors focused on the 6-4T neuroglioblast (NGB6-4T). This cell initially divides to give a neuroblast (which subsequently divides symmetrically to give two neurons), and a glioblast (which generates three glial cells). They showed that the mode of NGB6-4T division has several distinguishing features. First, the two cells produced by NGB6-4T division are quite similar in size, unlike those produced by the asymmetric division of neuroblasts. Also, whereas neuroblasts divide along the apico-basal axis of the neuroepithelium, the NGB6-4T cells divide obliquely, such that the glioblast daughter cell acquires a basal, anterior and medial position with respect to the neuroblast daughter cell. glide/gcm RNA accumulates in particles at the medio-basal anterior side of the cell during metaphase and it segregates into the glioblast daughter cell on division. The particulate distribution of the RNA is unusual in itself, as determinants that segregate during asymmetric cell division generally accumulate in a homogeneous crescent in the cell cortex.

Localization of glide/gcm depends on the Staufen and Miranda proteins, which also localize the Prospero (Pros) transcription factor. Pros co-segregates with glide/gcm, and pros mutant flies are deficient in all the glial progeny of the NGB6-4T. However, gain-of-function experiments showed that Pros is not sufficient to activate glide/gcm gene expression, and Ragone et al. propose that its role is to maintain glide/gcm expression in the daughter cell. The pros mutant CNS shows an increase in the number of cells expressing eagle , which is a characteristic of the neurons that arise from NGB6-4T. This indicates that daughter cells that fail to maintain glide/gcm expression revert to a neuronal cell fate.

So, NGB6-4T cells have a distinctive oblique mode of asymmetric cell division, during which glide/gcm becomes segregated into the daughter cell that will give rise to glia. After division, glide/gcm expression must be maintained in the daughter cell in order for gliogenesis to occur, and this maintenance requires the function of Prospero. This research hints at possible common mechanisms of asymmetric division in Drosophila cells that generate glia; for example, the PIIb cell, which produces a glial precursor in the peripheral nervous system, also divides obliquely. However, PIIb does not express glide/gcm before division, ruling out a causal relationship between expression of this determinant and the orientation of the mitotic spindle. It will be very interesting to find out what other characteristics are shared by gliogenic precursors in Drosophila.