In:
Genes & Development, Cold Spring Harbor Laboratory, Vol. 21, No. 20 ( 2007-10-15), p. 2593-2606
Abstract:
Phr1 is the single well-conserved murine ortholog of the invertebrate ubiquitin ligase genes highwire (in Drosophila ) and rpm-1 (in Caenorhabditis elegans ). The function and mechanism of action of highwire and rpm-1 are similar—both cell-autonomously regulate synaptogenesis by down-regulating the ortholog of the mitogen-activated protein kinase kinase kinase dual leucine zipper kinase (MAPKKK DLK). Here, using a targeted conditional mutant, we demonstrate that Phr1 also plays essential roles in mammalian neural development. As in invertebrates, Phr1 functions cell-autonomously to sculpt motor nerve terminals. In addition, Phr1 plays essential roles in the formation of major CNS axon tracts including those of the internal capsule, in part via cell-nonautonomous mechanisms, and these results reveal a choice point for cortical axons at the corticostriatal boundary. Furthermore, whereas the neurite morphology phenotypes of highwire and rpm-1 are suppressed by loss of DLK in flies and worms, Phr1 -dependent CNS defects persist in Phr1 , DLK double mutants. Thus, in the mammalian nervous system Phr1 is required for formation of major CNS axon tracts via a mechanism that is both cell-nonautonomous and independent of DLK .
Type of Medium:
Online Resource
ISSN:
0890-9369
,
1549-5477
Language:
English
Publisher:
Cold Spring Harbor Laboratory
Publication Date:
2007
detail.hit.zdb_id:
1467414-2
SSG:
12
