UNC5C is required for spinal accessory motor neuron development.

In both invertebrates and vertebrates, UNC5 receptors facilitate chemorepulsion away from a Netrin source. Unlike most motor neurons in the embryonic vertebrate spinal cord, spinal accessory motor neuron (SACMN) cell bodies and their axons translocate along a dorsally directed trajectory away from the floor plate/ventral midline and toward the lateral exit point (LEP). We have recently shown that Netrin-1 and DCC are required for the migration of SACMN cell bodies, in vivo. These observations raised the possibility that vertebrate UNC5 proteins mediate the presumed repulsion of SACMN away from the Netrin-rich ventral midline. Here, we show that SACMN are likely to express UNC5A and UNC5C. Whereas SACMN development proceeds normally in UNC5A null mice, many SACMN cell bodies fail to migrate away from the ventral midline and inappropriately cluster in the ventrolateral spinal cord of mouse embryos lacking UNC5C. These results support an important role for UNC5C in SACMN development.

Cloning and characterization of a Na+-driven anion exchanger (NDAE1). A new bicarbonate transporter.

Regulation of intra- and extracellular ion activities (e.g. H(+), Cl(-), Na(+)) is key to normal function of the central nervous system, digestive tract, respiratory tract, and urinary system. With our cloning of an electrogenic Na(+)/HCO(3)(-) cotransporter (NBC), we found that NBC and the anion exchangers form a bicarbonate transporter superfamily. Functionally three other HCO(3)(-) transporters are known: a neutral Na(+)/ HCO(3)(-) cotransporter, a K(+)/ HCO(3)(-) cotransporter, and a Na(+)-dependent Cl(-)-HCO(3)(-) exchanger. We report the cloning and characterization of a Na(+)-coupled Cl(-)-HCO(3)(-) exchanger and a physiologically unique bicarbonate transporter superfamily member. This Drosophila cDNA encodes a 1030-amino acid membrane protein with both sequence homology and predicted topology similar to the anion exchangers and NBCs. The mRNA is expressed throughout Drosophila development and is prominent in the central nervous system. When expressed in Xenopus oocytes, this membrane protein mediates the transport of Cl(-), Na(+), H(+), and HCO(3)(-) but does not require HCO(3)(-). Transport is blocked by the stilbene 4,4'-diisothiocyanodihydrostilbene- 2, 2'-disulfonates and may not be strictly electroneutral. Our functional data suggest this Na(+) driven anion exchanger (NDAE1) is responsible for the Na(+)-dependent Cl(-)-HCO(3)(-) exchange activity characterized in neurons, kidney, and fibroblasts. NDAE1 may be generally important for fly development, because disruption of this gene is apparently lethal to the Drosophila larva.