Figure 1. The embryonic origins and specification of the ASE neurons.

A: The early lineage of the C. elegans embryo leading to the formation of the five founder blastomeres (AB, MS, E, C and P₃). The pie-charts indicate the relative number of cells and tissue types that are produced from each founder blastomere. The majority of neurons, including ASE, descend form the AB blastomere. B: Lineage of the ASEL and ASER neurons indicating they descend from asymmetric lineage origins which first diverge at the AB²-cell stage (adapted from [6]). The Notch signal that specifies the difference between ABa and ABp blastomeres is indicated and leads to the down-regulation of tbx-37/tbx-38 (expression indicated in green) in the ABp lineage. This early lineage difference is crucial for the specification of ASE left-right asymmetry [12]. The molecular link between the expression of tbx-37/tbx-38 and the specification of ASE asymmetry is unclear. From the ABalpp/ABpraa stage onwards the lineage produces exclusively ectodermal tissue. From the ABalpppp/ABpraaap stage onwards the lineage produces exclusively neurons, including ASE. Purple asterisks indicate the point at which the proneural gene hlh-14, described in this paper, acts to regulate neuronal differentiation in the ASE lineage. C: Summary of the previously described bi-stable feedback loop that regulates ASE left-right asymmetry. The bi-stable feedback loop consists of both transcription factors and micro-RNAs and controls the expression of downstream terminal differentiation genes. All factors in the loop and the downstream terminal factors are regulated in addition by the ASE terminal selector che-1 (expression indicated in B in orange). The molecular link between the early lineage difference and the bi-stable feedback loop is not known. Brown asterisks indicate that the COMPASS histone-modifying complex, also identified in this paper, acts earlier than che-1 and before the birth of the ASE neurons to regulate lsy-6 expression and control ASE asymmetry.