Nogo‐B is the major form of Nogo at the floor plate and likely mediates crossing of commissural axons in the mouse spinal cord

    loading  Checking for direct PDF access through Ovid


In the developing spinal cord, commissural neurons in the dorsal horn send axons across the ventral midline and project to the brainstem and thalamus. After crossing the midline, the axons form the longitudinal fiber tracts of the anterolateral system. The growth of commissural axons has been shown to be directed by attractants and repellent molecules, produced as diffusible factors from the floor plate (Brankatschk & Dickson, 2006; Butler & Dodd, 2003; Sabatier et al., 2004). Attractant molecules such as Netrin‐1 and Sonic Hedgehog direct the initial course of commissural axons to the ventral midline (Kennedy, Serafini, de la Torre, & Tessier‐Lavigne, 1994; Tessier‐Lavigne, Placzek, Lumsden, Dodd, & Jessell, 1988). Netrin‐1 is a diffusible molecule secreted by the floor plate, which attracts axons at a long range through interaction with the receptors deleted in colorectal cancer and neogenin (Keino‐Masu et al., 1996; Xu et al., 2014). Once commissural axons enter the floor plate, they lose responsiveness to these attractant molecules and gain response to repulsive cues that are expressed strongly in the floor plate, which drive axons out from the floor plate and prevents recrossing. One of these factors is Semaphorin 3B, which has been shown to expel commissural axons from the floor plate through its receptor Neuropilin (Zou, Stoeckli, Chen, & Tessier‐Lavigne, 2000). Another repulsive cue is Slit, which prevents axons that have crossed the midline from recrossing, mainly through the interaction with Robo receptors on the axon (Long et al., 2004; Zou et al., 2000). However, blocking the function of either Semaphorin or Slit does not prevent all commissural axons leaving the floor plate, indicating that multiple mechanisms are operating.
Nogo is a myelin associated protein that belongs to the reticulon superfamily proteins. It exists in at least three known isoforms, Nogo‐A, ‐B, and ‐C (GrandPre, Nakamura, Vartanian, & Strittmatter, 2000). In the adult central nervous system (CNS), Nogo is found in the myelin sheath and cell bodies of oligodendrocytes (Huber, Weinmann, Brosamle, Oertle, & Schwab, 2002; Kuhlmann, Remington, Maruschak, Owens, & Bruck, 2007). Nogo's inhibitory action on axon regeneration after CNS injuries has been studied extensively. The inhibitory effects of Nogo act through binding to the Nogo receptor (NgR) complex (Domeniconi et al., 2002; Wang et al., 2002). However, Nogo is also expressed in subsets of neurons in the adult CNS (Cheatwood, Emerick, Schwab, & Kartje, 2008; Huber et al., 2002), indicating functions other than inhibiting axon growth.
In our recent studies, Nogo, in particularly Nogo‐B, was shown to be expressed by the radial glia at the midline of mouse chiasm (Wang, Chan, Taylor, & Chan, 2008b; Wang, Wang, Ma, Taylor, & Chan, 2016). It contributes to the bilateral routing of optic axons through differential regulation of NgR expression on the nasal and ventral temporal axons at the chiasm (Wang, Chan, Taylor, & Chan, 2008a). We have also shown that Nogo is expressed strongly on the radial glia at the ventral midline of mouse spinal cord when commissural axons are growing through the floor plate (Wang, Wang, Zhao, & Chan, 2010). The expression of NgR is spatially regulated, with a basal level on axons growing toward and navigating the floor plate, but at an elevated level on axons after crossing and joining the longitudinal tracts. This expression pattern suggests a role for Nogo in the post‐crossing phase. However, other studies have shown that Nogo is expressed largely in neurons and axons in the developing spinal cord rather than on glial cells (Caltharp et al., 2007; Huber et al., 2002; O'Neill, Whalley, & Ferretti, 2004), arguing against a role in axon guidance.

Related Topics

    loading  Loading Related Articles