The Caenorhabditis elegans lim-6 LIM homeobox gene regulates neurite outgrowth and function of particular GABAergic neurons

We describe here the functional analysis of the C, elegans LIM homeobox gen e lim-6, the ortholog of the mammalian Lmx-1a and b genes that regulate lim b, CNS, kidney and eye development. lim-6 is expressed in a small number of sensory-, inter- and motorneurons, in epithelial cells of the uterus and i n the excretory system. Loss of lim-6 function affects late events in the d ifferentiation of two classes of GABAergic motorneurons which control rhyth mic enteric muscle contraction. lim-6 is required to specify the correct ax on morphology of these neurons and also regulates expression of glutamic ac id decarboxylase, the rate limiting enzyme of GABA synthesis in these neuro ns. Moreover, lim-6 gene activity and GABA signaling regulate neuroendocrin e outputs of the nervous system, In the chemosensory system lim-6 regulates the asymmetric expression of a probable chemosensory receptor. lim-6 is al so required in epithelial cells for uterine morphogenesis. We compare the f unction of lim-6 to those of other LIM homeobox genes in C, elegans and sug gest that LIM homeobox genes share the common theme of controlling terminal neural differentiation steps that when disrupted lead to specific neuroana tomical and neural function defects.