Disease relevance of Unc5c

• Furthermore, a comparative expression analysis is presented with Unc5h3, deleted in colorectal cancer and Netrin-1 [1].

High impact information on Unc5c

• As Rcm is a member of a newly described family of vertebrate homologues of UNC-5 which are netrin-binding proteins, our results indicate that UNC-5-like proteins may have a conserved function in mediating netrin-guided migration [2].
• Mice homozygous for the spontaneous rostral cerebellar malformation mutation (rcm(s)) or a newly identified transgenic insertion allele (rcm(tg)) exhibit cerebellar and midbrain defects, apparently as a result of abnormal neuronal migration [2].
• We provide evidence that these two UNC-5 homologues, as well as the rcm gene product, are netrin-binding proteins, supporting the hypothesis that UNC-5 and its relatives are netrin receptors [3].
• A detailed analysis of the migratory defect in facial branchio-motoneurons reveals ectopic expression of the cell surface receptors Ret and Unc5h3 in premigratory neurons, but no changes in the rhombomeric environment [4].
• Our results suggest that Pax6 plays a strong role during hindbrain migration processes and at least part of its activity is mediated through regulation of the netrin receptor Unc5h3 [5].

Biological context of Unc5c

• To identify these modifier loci, we performed genome scans of the hybrid Unc5c(-/-) mice and found a major SJL-derived suppressor locus on Chromosome 17 [6].
• We demonstrate that the Unc5h3 gene product, shown previously to regulate cerebellar granule cell migrations, also controls the guidance of the corticospinal tract, the major tract responsible for coordination of limb movements [7].
• Last, interactions between the Dcc and Unc5h3 mutations were observed in gene dosage experiments [7].
• Embryonic phenotype of Unc5h3 mutant mice suggests chemorepulsion during the formation of the rostral cerebellar boundary [8].

Anatomical context of Unc5c

• Motor axon guidance of the mammalian trochlear and phrenic nerves: dependence on the netrin receptor Unc5c and modifier loci [6].
• Here, we demonstrate that mice with a null mutation in the netrin receptor Unc5c on the inbred C57BL/6J (B6) genetic background have ventral/ipsilateral trochlear nerve misprojections [6].
• Some granule cells are found in ectopic positions in the inferior colliculus which may result from the complete absence of Unc5h3 expression in Pax6(Sey)/Pax6(Sey) granule cells [5].
• Unc5h3 transcripts are expressed early (embryonic day 8.5) in the hindbrain region and later in the cerebellar primordia [8].
• However, at E13.5, an abnormal subpopulation of granule cell and Purkinje cell precursors becomes detectable in rostral areas of the Unc5h3 mutant brain stem [8].

Regulatory relationships of Unc5c

• Chimeric mice were made between wild-type ROSA26 transgenic mouse embryos (whose cells express beta-galactosidase) and Unc5h3 mutant embryos [9].
• Although 5'-untranslated regions typically house post-transcriptional elements, several lines of evidence indicated that Rhox5 down-regulates Unc5c at the transcriptional level [10].

Other interactions of Unc5c

• The mutation, called rostral cerebellar malformation, rcm, has been located on chromosome (Chr) 3 between the alcohol dehydrogenase-3 (Adh-3) complex and varitint waddler-J (VaJ) [11].

References