Fig 6. Regulation of Asymmetric NSM Neuroblast Division and the Apoptotic Death of the NSM sister Cell (A) Molecular models. (Wild type) By repressing the transcription of the Snail-related gene
ces-1, the proteins CES-2 HLF and DNJ-11 MIDA1 ensure that the CES-1 Snail protein is present at an appropriate, low level in the unpolarized, early NSM neuroblast. Blue oval indicates polarity factor that is required to establish polarity in the late NSM neuroblast and the synthesis of which is promoted by CES-1. Indicated in red is a complex that restricts the polarity factor to the ventral/medial side of the NSM neuroblast. Once localized to the ventral/medial side, the polarity factor is involved in restricting CES-1 to the ventral/medial side of the late NSM neuroblast. See text for details. (
dnj-11(lf),
ces-2(lf),
ces-1(gf)) Loss-of-function mutations of
dnj-11 or
ces-2, or a gain-of-function mutation of
ces-1 result in an increased level of CES-1 Snail protein in the early NSM neuroblast. This increased level of CES-1 protein results in a level of polarity factor too high to establish asymmetry and restrict CES-1 protein to the ventral/medial side. See text for details. (B) Genetic pathway.
dnj-11 acts upstream of or in parallel to
ces-2 to negatively regulate the function of
ces-1, thereby causing asymmetric NSM neuroblast division and NSM sister cell death.
ces-1 function can affect asymmetric NSM neuroblast division by regulating the function of a gene or genes required for the process. By negatively regulating
egl-1,
ces-1 function can also prevent the
hlh-2,
hlh-3-dependent death of the NSM sister cells.
ces-1 function in NSM sister cell death is affected by the process of asymmetric NSM neuroblast division, which causes the asymmetric distribution of the product of the
ces-1 gene. See text for details.