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We describe here the functional analysis of the C. elegans LIM homeobox gene lim-6, the ortholog of the mammalian Lmx-1a and b genes that regulate limb, 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 in the excretory system. Loss of lim-6 function affects late events in the differentiation of two classes of GABAergic motorneurons which control rhythmic enteric muscle contraction. lim-6 is required to specify the correct axon morphology of these neurons and also regulates expression of glutamic acid decarboxylase, the rate limiting enzyme of GABA synthesis in these neurons. Moreover, lim-6 gene activity and GABA signaling regulate neuroendocrine outputs of the nervous system. In the chemosensory system lim-6 regulates the asymmetric expression of a probable chemosensory receptor. lim-6 is also required in epithelial cells for uterine morphogenesis. We compare the function of lim-6 to those of other LIM homeobox genes in C. elegans and suggest that LIM homeobox genes share the common theme of controlling terminal neural differentiation steps that when disrupted lead to specific neuroanatomical and neural function defects.

We show here that the lin-11 LIM homeobox gene is expressed in nine classes of head, ventral cord, and tail neurons and functions at a late step in the development of a subset of these neurons. In a lin-11 null mutant, all lin-11-expressing neurons are generated. Several of these neurons, however, exhibit neuroanatomical as well as functional defects. In the lateral head ganglion, lin-11 functions in a neural network that regulates thermosensory behavior. It is expressed in the AIZ interneuron that processes high temperature input and is required for the function of AIZ in the thermoregulatory neural network. Another LIM homeobox gene, ttx-3, functions in the antagonistic thermoregulatory interneuron AIY (). Thus, distinct LIM genes specify the functions of functionally related antagonistic interneurons within a neural network dedicated for thermoregulatory processes. Both ttx-3 and lin-11 expression are maintained throughout adulthood, suggesting that these LIM homeobox genes play a role in the functional maintenance of this neural circuit. We propose that particular LIM homeobox genes specify the distinct features of functionally related neurons that generate patterned behaviors.