unc-40 is required to guide ventrally and dorsally- oriented cell and growth cone (GC) migrations in C. elegans. These migrations are oriented by graded expression of the UNC- 6 path cue molecule along the D/V axis (1995 MTG ABS. p.15).
unc-40 encodes an integral membrane receptor (1995 MTG ABS. p.16) related to the human protein DCC (deleted in colorectal cancer) and the chick neogenin gene, both of which are expressed in growing neurons. We have made transgenic animals that express GFP under the control of the
unc-40 regulatory region to get some idea of where UNC-40 protein may be expressed in the nematode. The regulatory region used contains 0.7 kb of sequence 5' to the initiator methionine in exon 1, plus exons 1-3, introns 1-2 and part of intron 3 (total 3.5 kb). The 0.7 kb of sequence 5' to the initiator codon alone does not appear to drive full expression of GFP suggesting that exons 1-3 and/or introns 1-3 contain regulatory elements essential for full expression. The
unc-40-GFP transgenic animals express in all neurons whose axons are known to be misguided in
unc-40 mutants and in a number of mesodermal cells whose migrations are affected. Expression has been observed in all motorneurons in the ventral cord; most intensely in those that grow to the dorsal side. Expression also occurs in a number of sensory neurons including several that extend pioneer axons ventrally on the epidermis. These include AVM, PVM, HSN, PVD,PHA, PHB (and probably ADE and PDE), as well as 2-3 unidentified lumbar neurons. The hermaphrodite distal tip cells also stain very early in their first phase longitudinal migration, well before
unc-5-GFP expression occurs (see abstract by Su et al., this issue). Additional glowing cells include CANs, at least one neuron in the pharynx, at least one pair of labial neurons (IL1, IL2, OLQ and/or OLL), at least one pair of monopolar ring interneurons (possibly RIM, RIC, or AVB), phasmid and postdeirid sensillar support cells (sheath and socket cells), and several yet unidentified neurons in the head and tail. The excretory cell also stains in many animals and some body muscles stain very faintly and variably. Vulval muscles stain intensely and reproducibly. The pattern of neuronal staining observed overlaps so thoroughly with the spectrum of cells affected by
unc-40 mutations that it is tempting to speculate that it reflects the real pattern of
unc-40 expression. If this is true, it would imply that UNC-40 is a receptor expressed on cells or pioneer axon GCs that migrate dorsally or ventrally on the epidermis. It may act with UNC-5 receptor in dorsally migrating cells and GCs to mediate avoidance responses to ventral concentrations of UNC-6 and in ventrally migrating cells and GCs to mediate attractive responses to UNC-6.