Distinct Mechanisms Triggering Glial Differentiation in Drosophila Thoracic and Abdominal Neuroblasts 6-4

Abstract

Neurons and glia are produced in stereotyped patterns after neuroblast cell division during development of the Drosophila central nervous system. The first cell division of thoracic neuroblast 6-4 (NB6-4T) is asymmetric, giving rise to a glial precursor cell and a neuronal precursor cell. In contrast, abdominal NB6-4 (NB6-4A) divides symmetrically to produce two glial cells. To understand the relationship between cell division and glia-neuron cell fate determination, we examined and compared the effects of known cell division mutations on the NB6-4T and NB6-4A lineages. Based on observation of expression of glial fate determination and early glial differentiation genes, the onset of glial differentiation occurred in NB6-4A but not in NB6-4T when both cell cycle progression and cytokinesis were genetically arrested. On the other hand, glial differentiation started in both lineages when cytokinesis was blocked with intact cell cycle progression. These results showed that NB6-4T, but not NB6-4A, requires cell cycle progression for acquisition of glial fate, suggesting that distinct mechanisms trigger glial differentiation in the different lineages.

Genetic mechanisms regulating proliferation and cell specification in the Drosophila embryonic CNS

“…Analogous results had been observed in NB4-6T, which give rise to a neural and a glial precursor cell, where expression of Gcm within the glial precursor cell is dependent on the S-phase progression [122][123][124].…”

Stem cell aging and plasticity in the Drosophila nervous system

“…The string mutation blocks cells in the G 0 phase before the first NB division. 37,38 Our data formally demonstrate that non-dividing NBs can be converted into glia, indicating that plasticity is not related to cell division. Direct conversion or reprogramming of different cell types arrested in the G 0 phase has been documented in other cases as well.…”

Cyclin E Acts under the Control of Hox-Genes as a Cell Fate Determinant in the Developing Central Nervous System

“…In this situation the thoracic NB6-4, although expressing genes for glial determination like gcm and prospero, does not take over glial fate, as can be seen by lack of expression of the glial differentiation marker Repo. 18,23,24 In contrast to this, the abdominal NB6-4 gives rise to a glial cell. 23 Since CycE is only expressed in the thoracic precursor it appears to be sufficient to confer neuronal cell fate to NB6-4 also in the absence of divisions.…”

“…18,23,24 In contrast to this, the abdominal NB6-4 gives rise to a glial cell. 23 Since CycE is only expressed in the thoracic precursor it appears to be sufficient to confer neuronal cell fate to NB6-4 also in the absence of divisions.…”

“…During the first division of the thoracic NB6-4t neuroglioblast, the cell-fate determinant Prospero 19,20 is asymmetrically localized and segregates preferentially to the daughter destined to become a glioblast; here it maintains high levels of expression of the glial determinant Glial cells missing (GCM). [21][22][23][24] This glioblast will produce three glial cells whereas its sibling, which does not inherit Prospero, will give rise to four to six interneurons. 9 By contrast, the abdominal NB6-4a neuroblast divides symmetrically to produce two daughters, both of which are Prospero-positive and adopt a glial fate.…”