A lateral signaling event diversifies the cell fates of the left and right pair of AWC olfactory neurons. The two AWC neurons take on distinct cell fates that are distinguished by expression of
str-2::GFP , a reporter gene fusion to a candidate odorant receptor. The choice to express
str-2 is random, but coordinated; about half of the animals express
str-2 in the left neuron and about half of the animals express it in the right, but each animal expresses
str-2 in exactly one AWC neuron. AWC cells fail to express
str-2 in animals with defects in axon guidance or with one AWC ablated early in development, suggesting that communication between the two neurons may be necessary for the signaling event (Troemel et al., 1999). The decision between the
str-2 expressing (AWC ON ) and the non-
str-2 expressing (AWC OFF ) fates is mediated by a calcium signal via the UNC-2 and UNC-36 calcium channel subunits, UNC-43/CAMKII (Troemel et al., 1999), the MAPKKK NSY-1 (Sagasti et al., 2001), and the MAPKK SEK-1 (Tanaka-Hino et al., 2002), resulting in repression of the AWC ON fate and induction of the AWC OFF fate. However, upstream regulators of the AWC asymmetry pathway are not known. To understand the early steps in AWC diversification, we performed a screen for neuronal symmetry (nsy) mutants with two AWC OFF cells. This phenotype is expected when communication between the two AWC cells is disrupted. The screen identified genes involved in AWC development as well as the maintenance of
str-2 expression. Mutations in six new genes were isolated:
ceh-36,
nsy-4,
nsy-5,
nsy-6,
nsy-7, and
nsy-8 . The mutants were classified based on their patterns of axon guidance, expression of AWC-specific reporters, and chemotaxis to AWC OFF and AWC ON -sensed odorants (Wes and Bargmann, 2001), and placed in the genetic pathway for AWC development using epistasis analysis.
nsy-4 and
nsy-5 are of particular interest, as they act upstream of the calcium activated MAP kinase pathway.
nsy-4 encodes a novel transmembrane protein. We are using cell specific expression to determine the role of NSY-4 in regulation of this signaling pathway. Sagasti A, Hisamoto N, Hyodo J, Tanaka-Hino M, Matsumoto K, Bargmann CI. Cell. 2001 Apr 20;105(2):221-32. Tanaka-Hino M, Sagasti A, Hisamoto N, Kawasaki M, Nakano S, Ninomiya-Tsuji J, Bargmann CI, Matsumoto K. EMBO 2002 Jan;3(1):56-62. Troemel ER, Sagasti A, Bargmann CI. Cell. 1999 Nov 12;99(4):387-98. Wes PD, Bargmann CI. Nature. 2001 Apr 5;410(6829):698-701.