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Background  The  Notch  pathway functions repeatedly during the development of the central nervous system in metazoan organisms to control cell fate and regulate cell proliferation and asymmetric cell divisions. Within the  Drosophila  midline cell lineage, which bisects the two symmetrical halves of the central nervous system,  Notch  is required for initial cell specification and subsequent differentiation of many midline lineages.    Methodology/Principal Findings  Here, we provide the first description of the role of the  Notch  co-factor,  mastermind , in the central nervous system midline of  Drosophila . Overall, zygotic  mastermind  mutations cause an increase in midline cell number and decrease in midline cell diversity. Compared to mutations in other components of the  Notch  signaling pathway, such as  Notch  itself and  Delta , zygotic mutations in  mastermind  cause the production of a unique constellation of midline cell types. The major difference is that midline glia form normally in zygotic  mastermind  mutants, but not in  Notch  and  Delta  mutants. Moreover, during late embryogenesis, extra anterior midline glia survive in zygotic  mastermind  mutants compared to wild type embryos.    Conclusions/Significance  This is an example of a mutation in a signaling pathway cofactor producing a distinct central nervous system phenotype compared to mutations in major components of the pathway.

Mastermind Mutations Generate a Unique Constellation of Midline Cells within the Drosophila CNS