Reelin signaling is necessary for a specific step in the migration of hindbrain efferent neurons

Abstract

The cytoarchitecture of the hindbrain results from precise and co-ordinated sequences of neuronal migrations. Here, we show that reelin, an extracellular matrix protein involved in neuronal migration during CNS development, is necessary for an early, specific step in the migration of several hindbrain nuclei. We identified two cell populations not previously known to be affected in reeler mutants that show a common migratory defect: the olivocochlear efferent neurons and the facial visceral motor nucleus. In control embryos, these cells migrate first toward a lateral position within the neural tube, and then parallel to the glial cell processes, to a ventral position where they settle close to the pial surface. In reelermutants, the first migration is not affected, but the neurons are unable to reach the pial surface and remain in an ectopic position. Indeed, this is the first evidence that the migration of specific hindbrain nuclei can be divided into two parts: a reelin-independent and a reelin-dependent migration. We also show that reelin is expressed at high levels at the final destination of the migratory process, while the reelin intracellular effector Dab1 was expressed by cell groups that included the two populations affected. Mice mutant at the Dab1 locus, called scrambler, exhibit the same phenotype, a failure of final migration. However, examination of mice lacking both reelin receptors, ApoER2 and VLDLR, did not reveal the same phenotype, suggesting involvement of an additional reelin-binding receptor. In the hindbrain, reelin signaling might alter the adhesive properties of efferent neurons and their ability to respond to directional cues, as has been suggested for the migration of olfactory bulb precursors.

Trio Controls the Mature Organization of Neuronal Clusters in the Hindbrain

“…Nevertheless, reelin could act in partnership with various receptors. Among them, apolipoprotein E receptor 2/very-low-density lipoprotein receptor (Rossel et al, 2005) and cadherin-related neuronal receptors family of protocadherins (Jossin, 2004) were recently proposed. To date, no reelin expression has been detected in ION (Schiffmann et al, 1997), and the expression domain of protocadherins in the developing hindbrain has been poorly investigated.…”

Reelin provides an inhibitory signal in the migration of gonadotropin-releasing hormone neurons

“…The presence of a normal complement of GnRH-secreting neurons in the hypothalamus of mutants lacking both lipoprotein receptors and in scrambler mice lacking Dab1 is consistent with the in vitro findings. Although we are at present unable to identify a mechanism that mediates the action of reelin in this neurendocrine system, it is worth noting that effects of reelin, independent of the conventional reelin signalling pathway, have recently been described (Rossel et al, 2005) in the developing mouse hindbrain. These authors identified a ventral reelin-dependent migration that is independent of the receptors, ApoER2 and Vldlr.…”

Frizzled3a and Celsr2 function in the neuroepithelium to regulate migration of facial motor neurons in the developing zebrafish hindbrain

“…In the mammalian cortex, neurons are generated in ventricular germinal zones and migrate radially towards the pial surface to form architectural layered structures. In mouse embryos, Reelin signaling regulates the positioning of neurons during layer formation of the cerebrum (reviewed by Tissir and Goffinet, 2003), and is essential for radial migration of the nVII motor neurons (Ohshima et al, 2002;Rossel et al, 2005). These data suggest that similar mechanisms regulate the proper positioning of both the hindbrain motor neurons and the cortical layer neurons.…”

“…In mouse hindbrain, guidance cues emanate from r5 and r6 to attract the nVII motor neurons (Studer, 2001). These may include Reelin (Ohshima et al, 2002;Rossel et al, 2005) and Sdf-1 (Sapede et al, 2005) signaling. In the present study, we have clearly shown that the neuroepithelial cells function in preventing integration of the nVII motor neurons into the neuroepithelial layer of the hindbrain, and that this radial exclusion is essential for normal migration of the nVII motor neurons.…”