Research Highlights

Neuronal development: A notch up with N-acetylglucosamine

Mutations in Fng (right) cause defects of Pros expression (magenta color)

Reproduced with permission of the Company of Biologists

Glycosylation of the extracellular domain of the Notch receptor by monosaccharides such as fucose is required for Notch receptor signaling. The glycosyltransferase Fringe attaches N–acetylglucosamine to the fucose residues of Notch. Notch signaling occurring after Fringe's involvement has been shown to determine boundary formation and cell polarity in Drosophila. Now, Thomas and van Meyel report in Development that Notch glycosylation by Fringe is also required for the expression of the transcription factor Prospero (Pros) in a subpopulation of longitudinal glia (LG) cells that are in close contact with the axons of developing neurons. Pros is necessary for the LG cells to retain their mitotic potential for further development and repair of the central nervous system (CNS).

The authors observed the presence of Fringe mRNA in the anteriormost subpopulation of LG cells in each segment of the embryonic CNS. To elucidate the consequences of Fringe absence, Thomas and van Meyel examined flies carrying various Fringe mutations. While the number of LG cells remained unchanged, expression of Pros in the anteriormost subpopulation was significantly reduced. This suggests that Pros was active in the LG precursor cells to drive their proliferation, so that LG cells could sheath developing neuronal axons. Afterwards, the actions of Fringe are necessary to maintain Pros expression in the glia cells.

The authors went on to find that Notch is expressed in the LG membrane and hypothesize that glycosylation of Notch — which alters its sensitivity to ligands — may be responsible for Pros expression. To confirm this, Thomas and van Meyel misexpressed either Notch or Fringe in all LG cells and observed additional LG cells expressing Pros. They also observed a similar effect when overexpressing the Notch ligand Delta in neurons whose axons are in contact with the glia cells. Thus, the authors hypothesize that in wild-type Drosophila, neuronal axons projecting towards the anterior LG express Delta, which interacts with Fringe-glycosylated Notch. This releases the intracellular domain of Notch and initiates Pros expression in the anteriormost LG cell subpopulation.

The study of Thomas and van Meyel is the first evidence that the actions of the glycosyltransferase Fringe participate in the CNS development of Drosophila. In the CNS of mice, Lunatic Fringe is expressed in glia precursors during development and in subpopulations of glia cells in the mature brain. Fringe glycosyltransferases might have an evolutionarily conserved role in sensitizing glia cell subclasses to Notch signaling from neurons.

Author: Mirko von Elstermann