Spinal Motor Neuron Migration and the Significance of Topographic Organization in the Nervous System

Abstract

The nervous system displays a high degree of topographic organisation such that neuronal soma position is closely correlated to axonal trajectory. One example of such order is the myotopic organisation of the motor system where spinal motor neuron position parallels that of target muscles. This chapter will discuss the molecular mechanisms underlying motor neuron soma positioning, which include transcriptional control of Reelin signaling and cadherin expression. As the same transcription factors have been shown to control motor axon innervation of target muscles, a simple mechanism of topographic organisation specification is becoming evident raising the question of how coordinating soma position with axon trajectory might be important for nervous system wiring and its function.

Parallel Pbx -Dependent Pathways Govern the Coalescence and Fate of Motor Columns

“…Expression of Lhx1 in the lateral division of the LMC defines MNs that project to the dorsal limb compartment (Kania, 2014), and this population of Lhx1 + , Foxp1 + neurons was depleted in Pbx MNΔ mutants (Figure 2C,D). Within the LMC, neurons targeting individual limb muscles segregate into MN pools, some of which can be defined by expression of specific transcription factors.…”

“…We reasoned genes which facilitate the segregation and clustering of MMC and non-MMC populations would be specifically lost in Pbx mutants, but maintained under conditions where columnar segregation is preserved, such as in Foxp1 mutants. We screened over two dozen genes, including members of the cadherin and ephrin/Eph genes families, which have been implicated in neuronal migration and clustering within the hindbrain and spinal cord (Kania, 2014). This analysis identified a number of motor pool-restricted genes that are diminished in Pbx MNΔ mice, although the majority of these genes were also downregulated in Foxp1 mutants (Figure S5A–E and data not shown).…”

“…In tetrapods MNs projecting to functionally-related peripheral targets cluster into columnar and pool groups, establishing a central somatotopic map of peripheral innervation (Kania, 2014; Levine et al, 2012). The topographical organization of MNs can be revealed at a molecular level by expression of certain classes of transcription factors including Hox, Lim HD, and Foxp1 proteins (Dasen et al, 2008; Tsuchida et al, 1994).…”

“…Reelin and its receptor Disabled play essential roles in the migration and final positioning of LMC and PGC subtypes, and are downstream targets of Foxp1 and Lhx1 (Palmesino et al, 2010). In mice lacking Reelin or Disabled neurons occupy inappropriate positions within the spinal cord but are otherwise well clustered (Kania, 2014). The transcription factor Pea3 is necessary for the organization of MNs targeting the cutaneous maximus (CM) muscle, and in Pea3 mutants CM neurons are interspersed with MN pools occupying the same segment.…”

“…The ordered spatial relationship between neuronal position and target specificity is a prominent anatomical feature of primary sensory and motor systems, including the retinotectal map of the visual system and the somatotopic representation of the body surface within the cortex (Kania, 2014; Levine et al, 2012). While topographical maps appear to be critical in establishing appropriate connectivity and functionality within neural circuits, the underlying genetic mechanisms governing their formation are poorly understood.…”