The mouse rostral cerebellar malformation gene encodes an UNC-5-like protein.
Migration of neurons from proliferative zones to their functional sites is fundamental to the normal development of the central nervous system. 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. Laminar structure abnormalities in lateral regions of the rostral cerebellar cortex have been described in homozygous rcm(s) mice. We now demonstrate that the cerebellum of both rcm(s) and rcm(tg) homozygotes is smaller and has fewer folia than in the wild-type, ectopic cerebellar cells are present in midbrain regions by three days after birth, and there are abnormalities in postnatal cerebellar neuronal migration. We have cloned the rcm complementary DNA, which encodes a transmembrane receptor of the immunoglobulin superfamily. The sequence of the rcm protein (Rcm) is highly similar to that of UNC-5, a Caenorhabditis elegans protein that is essential for dorsal guidance of pioneer axons and for the movement of cells away from the netrin ligand, which is encoded by the unc-6 gene. 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.
Ackerman
S L
SL
The Jackson Laboratory, Bar Harbor, Maine 04609, USA. sla@aretha.jax.org
Kozak
L P
LP
Przyborski
S A
SA
Rund
L A
LA
Boyer
B B
BB
Knowles
B B
BB
D000595:Amino Acid Sequence; D000818:Animals; D015152:Blotting, Northern; D029742:Caenorhabditis elegans Proteins; D002455:Cell Division / Q000502:physiology; D002465:Cell Movement / Q000502:physiology; D002531:Cerebellum / Q000002:abnormalities / Q000196:embryology / Q000378:metabolism; D003001:Cloning, Molecular; D015870:Gene Expression; D015801:Helminth Proteins / Q000737:chemistry*; D006720:Homozygote; D017403:In Situ Hybridization; D008565:Membrane Proteins / Q000737:chemistry*; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D008969:Molecular Sequence Data; D009154:Mutation; D009414:Nerve Growth Factors / Q000378:metabolism; D000075386:Netrin Receptors; D000075388:Netrin-1; D009474:Neurons / Q000502:physiology; D016133:Polymerase Chain Reaction; D011956:Receptors, Cell Surface; D017978:Receptors, Growth Factor / Q000737:chemistry*; D017475:Receptors, Nerve Growth Factor / Q000737:chemistry / Q000235:genetics* / Q000502:physiology; D017386:Sequence Homology, Amino Acid; D014018:Tissue Distribution; D025521:Tumor Suppressor Proteins
D029742:Caenorhabditis elegans Proteins; D015801:Helminth Proteins; D008565:Membrane Proteins; D009414:Nerve Growth Factors; D000075386:Netrin Receptors; D011956:Receptors, Cell Surface; D017978:Receptors, Growth Factor; D017475:Receptors, Nerve Growth Factor; D025521:Tumor Suppressor Proteins; C105653:Unc5c protein, mouse; C077588:UNC-5 protein, C elegans; D000075388:Netrin-1