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2015 ; 5
(8
): 1567-74
Nephropedia Template TP
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SDN-1/Syndecan Acts in Parallel to the Transmembrane Molecule MIG-13 to Promote
Anterior Neuroblast Migration
#MMPMID26022293
Sundararajan L
; Norris ML
; Lundquist EA
G3 (Bethesda)
2015[May]; 5
(8
): 1567-74
PMID26022293
show ga
The Q neuroblasts in Caenorhabditis elegans display left-right asymmetry in their
migration, with QR and descendants on the right migrating anteriorly, and QL and
descendants on the left migrating posteriorly. Initial QR and QL migration is
controlled by the transmembrane receptors UNC-40/DCC, PTP-3/LAR, and the Fat-like
cadherin CDH-4. After initial migration, QL responds to an EGL-20/Wnt signal that
drives continued posterior migration by activating MAB-5/Hox activity in QL but
not QR. QR expresses the transmembrane protein MIG-13, which is repressed by
MAB-5 in QL and which drives anterior migration of QR descendants. A screen for
new Q descendant AQR and PQR migration mutations identified mig-13 as well as
hse-5, the gene encoding the glucuronyl C5-epimerase enzyme, which catalyzes
epimerization of glucuronic acid to iduronic acid in the heparan sulfate side
chains of heparan sulfate proteoglycans (HSPGs). Of five C. elegans HSPGs, we
found that only SDN-1/Syndecan affected Q migrations. sdn-1 mutants showed QR
descendant AQR anterior migration defects, and weaker QL descendant PQR migration
defects. hse-5 affected initial Q migration, whereas sdn-1 did not. sdn-1 and
hse-5 acted redundantly in AQR and PQR migration, but not initial Q migration,
suggesting the involvement of other HSPGs in Q migration. Cell-specific
expression studies indicated that SDN-1 can act in QR to promote anterior
migration. Genetic interactions between sdn-1, mig-13, and mab-5 suggest that
MIG-13 and SDN-1 act in parallel to promote anterior AQR migration and that SDN-1
also controls posterior migration. Together, our results indicate previously
unappreciated complexity in the role of multiple signaling pathways and inherent
left-right asymmetry in the control of Q neuroblast descendant migration.