Figure 9.

Transcriptional cascade regulating ASE(L/R) asymmetry. (A) Summary of expression of transcription factors and their effectors in ASE(L/R). Circles indicate gfp expressing (green)/nonexpressing (not filled) ASEL and ASER cells. The ASE(L/R) patterns of expression of ubiquitously expressed genes (unc-37 and lin-49) are not shown. Notes: ¹Low levels of cog-1 activity in ASEL are inferred from reporter gene assays as well as the observation that cog-1 is required in ASEL in a ceh-36 mutant to repress lim-6 expression. ²lim-6 is not required to initiate its own expression but to maintain it (data not shown); the empty circles refer to expression in the adult, after autoregulation has been established. ³flp-6::gfp was used to assess bilaterally symmetric ASE fate. ⁴See Figure 7C for an explanation of the reappearance of ASE asymmetry. (B) A molecular model for the establishment of asymmetric gcy-5 and gcy-7 expression. Arrows reflect genetic pathway interactions, which subsume either a direct interaction of a protein with the respective transcriptional regulatory elements or the presence of intermediary factors. Different sizes of the COG-1 protein in ASEL versus ASER are meant to reflect different protein levels brought about by differential activation or repression of cog-1 transcription (model #1 or model #2, which are not mutually exclusive). Note that low levels of cog-1 must be present in ASEL because, in a ceh-36 and lin-49 mutant background, a role for cog-1 is revealed in ASEL (Fig. 7). Differential expression of COG-1 in ASEL and ASER is either achieved through differential transcriptional repression in ASEL (model #1) or differential transcriptional activation in ASER (model #2). Because the loss of lim-6 results in activation of gcy-5 expression, we invoke CHE-1 as a potential direct positive regulator of gcy-5 expression, a notion supported by ectopically expressed CHE-1 being able to induce gcy-5 expression (data not shown; Uchida et al. 2003). We and others have also shown that CHE-1 regulates bilaterally symmetric features of ASE fate (Uchida et al. 2003; this paper). CEH-36 and LIN-49 do not regulate these features (data not shown).