Reelin Signaling in the Migration of Ventral Brain Stem and Spinal Cord Neurons

Abstract

The extracellular matrix protein Reelin is an important orchestrator of neuronal migration during the development of the central nervous system. While its role and mechanism of action have been extensively studied and reviewed in the formation of dorsal laminar brain structures like the cerebral cortex, hippocampus, and cerebellum, its functions during the neuronal migration events that result in the nuclear organization of the ventral central nervous system are less well understood. In an attempt to delineate an underlying pattern of Reelin action in the formation of neuronal cell clusters, this review highlights the role of Reelin signaling in the migration of neuronal populations that originate in the ventral brain stem and the spinal cord.

Correct setup of the substantia nigra requires Reelin-mediated fast, laterally-directed migration of dopaminergic neurons

“…Phosphorylated DAB1 then mediates Reelin signaling by regulating cell adhesive properties or cytoskeletal stability (Howell et al, 1997; Franco et al, 2011; Chai et al, 2009). In mice homozygous for null alleles of Reelin ( reeler ) or Dab1 (scrambler or Dab1 null ), in Vldlr/Apoer2 double knockout mice (Nishikawa et al, 2003; Kang et al, 2010; Sharaf et al, 2013), or in organotypic slices in which Reelin signaling is blocked, SN-mDA neurons do not reach their final positions in the ventrolateral midbrain and accumulate instead in the area of the lateral VTA (Bodea et al, 2014; Vaswani and Blaess, 2016). Whether Reelin affects tangential (lateral) mDA neuronal migration directly, or whether the failure of SN-mDA neurons to reach their final position in Reelin pathway mutants is due to alterations in glia fibers or neighboring neuronal populations has not been explored.…”

Netrin1/DCC signaling promotes neuronal migration in the dorsal spinal cord

“…Within the developing spinal cord, the molecular mechanism underlying the migration of neuroprogenitors and differentiated neurons is mostly uncharacterized. The Reelin/VLDLR/ApoER2 pathway has been shown to regulate the migration of certain populations in the ventral spinal cord [33]. Our previous study reveals that DCC is important for the migration of the dorsal neuroprogenitors and interneurons [4].…”

Dynamics, nanomechanics and signal transduction in reelin repeats

“…have indicated that RELN directly promotes N-cadherin-dependent neuronal adhesion, causing neuronal aggregation 17 . Thus RELN, through relaying biological signals, is a major player in brain development and functioning 18 . It also has numerous functions outside neuronal tissues: there is a mounting evidence that reelin signaling mechanisms may promote migration of cancer cells 11 .…”