[Abstract Title]. - Society for Neuroscience

Poster
230. Cell Migration: Molecules Mediating Migration
Time: Sunday, November 16, 2008, 1:00 pm - 5:00 pm
Program#/Poster#: 230.10/A36
Topic: A.02.c. Cell migration
Support: NSF Grant 0518714
Title: Aberrant migration of sympathetic preganglionic neurons into the dorsal root ganglia of
reeler and dab1KO mutants
Authors: J. M. HAN 1 , M. HIROSE 1 , A. I. BASBAUM 2 , *P. E. PHELPS 1 ;
1 Dept Physiological Sci., UCLA, Los Angeles, CA; 2 Depts Anat. and Physiol., UCSF, San
Francisco, CA
Abstract: Reelin is an extracellular matrix protein that is a critical contributor to cell positioning
during development. Deletion of Reelin in reeler mice disrupts the Reelin-Disabled-1 (Dab1)
signaling pathway, leading to the accumulation of high levels of Dab1 in neurons that migrate
incorrectly in reeler mutants. The first neurons found to be mispositioned in reeler spinal cord
were sympathetic preganglionic neurons (SPNs); they failed to stop in the intermediolateral horn
and instead continued to migrate medially. Here we describe an aberrant migration of Dab1labeled
spinal cord neurons into the PNS of embryonic reeler mice. These ectopic neurons
migrated along the reeler ventral root and into the ventral aspect of the dorsal root ganglia
(DRG) and the mixed spinal nerve. As we found these neurons only at thoracic and upper lumbar
segmental levels we suspected that they were SPNs. To test this hypothesis we used antibodies to
choline acetyltransferase (ChAT) and neuronal nitric oxide (nNOS), co-expressed by SPNs, and
found ectopically located neuronal clusters in reeler DRG. The mispositioned neurons increased
in number within the DRG between E12.5 and E14.5, decreased significantly by E17.5 and were
absent in adult reeler DRG. ChAT and nNOS double labeling experiments found a small number
of ChAT-only possible somatic motor neurons but most ectopic neurons expressed both ChAT
and nNOS, consistent with a SPN identity. To unequivocally identify these neurons as displaced
SPNs, we injected DiI into the sympathetic chain ganglia of reeler organotypic slices and found
retrogradely-labeled neuronal clusters in the mutant, but not the control, DRG. To determine if
the peripheral migratory errors were due to a loss of the Reelin-Dab1 signaling pathway, we
asked if dab1ko mice had similar ectopic neurons. At E14.5, both ChAT and nNOS-positive
neurons were in the ventral dab1ko mutant DRG, but not in dab1ko adult DRG. We conclude
that most of the aberrant neurons that erroneously migrate out of the spinal cord into the
periphery are SPNs. As these neurons die perinatally, the Reelin-Dab1 signaling pathway most
likely contributes to both their positioning and survival. These results indicate that Reelin
functions as a stop signal that prevents SPNs from migrating out of the CNS and maintains them
in the intermediolateral horn.