SEK‐1 MAPKK mediates Ca2+ signaling to determine neuronal asymmetric development in Caenorhabditis elegans

Abstract
The mitogen‐activated protein kinase (MAPK) pathway is a highly conserved signaling cascade that converts extracellular signals into various outputs. In Caenorhabditis elegans , asymmetric expression of the candidate odorant receptor STR‐2 in either the left or the right of two bilaterally symmetrical olfactory AWC neurons is regulated by axon contact and Ca2+ signaling. We show that the MAPK kinase (MAPKK) SEK‐1 is required for asymmetric expression in AWC neurons. Genetic and biochemical analyses reveal that SEK‐1 functions in a pathway downstream of UNC‐43 and NSY‐1, Ca2+/calmodulin‐dependent protein kinase II (CaMKII) and MAPK kinase kinase (MAPKKK), respectively. Thus, the NSY‐1–SEK‐1–MAPK cascade is activated by Ca2+ signaling through CaMKII and establishes asymmetric cell fate decision during neuronal development.