Abstract
In the vertebrate retina, the formation of neural circuits within discrete laminae is critical for the establishment of retinal visual function. Precise formation of retinal circuits requires the coordinated actions of adhesive and repulsive molecules, including repulsive transmembrane semaphorins (Sema6A, Sema5A, and Sema5B). These semaphorins signal through different Plexin A (PlexA) receptors, thereby regulating distinct aspects of retinal circuit assembly. Here, we investigate the physiological roles of three Class 6 transmembrane semaphorins (Sema6B, Sema6C, and Sema6D), previously identified as PlexA receptor ligands in non-retinal tissues, in mammalian retinal development. We performed expression analysis and also phenotypic analyses of mice that carry null mutations in each of genes encoding these proteins using a broad range of inner and outer retinal markers. We find that these Class 6 semaphorins are uniquely expressed throughout postnatal retinal development in specific domains and cell types of the developing retina. However, we do not observe defects in stereotypical lamina-specific neurite stratification of retinal neuron subtypes in Sema6B−/− or Sema6C−/−; Sema6D−/− retinas. These findings indicate these Class 6 transmembrane semaphorins are unlikely to serve as major PlexA receptor ligands for the assembly of murine retinal circuit laminar organization.
Highlights
Nervous system function relies in part on precise patterns of synaptic connectivity established during development
Previous studies show that these class 6 transmembrane semaphorins signal through the Plexin A (PlexA) receptors to regulate neural and non-neural development [7,8,9,10]
We recently found that Sema6A and several PlexA receptors play critical roles in regulating the development of retinal circuits [4,5,6], and we hypothesized that these class 6 transmembrane semaphorins might function through PlexA receptors to regulate retinal development
Summary
Nervous system function relies in part on precise patterns of synaptic connectivity established during development. External visual information is processed by distinct subtypes of retinal neurons that elaborate and establish synaptic connections within discrete laminae: the outer plexiform layer (OPL) and sublaminae of the inner plexiform layer (IPL). Sema5A and Sema5B signal through PlexA1 and PlexA3 to prevent neurites of multiple inner retinal neuron subtypes from aberrantly misprojecting into the outer retina, thereby constraining these neurites within the inner retina [4]. Taken together, these findings demonstrate that the PlexA receptors play critical roles in the formation of retinal circuits. It is not known whether PlexA receptor ligands previously identified in non-retinal tissues contribute to the retinal circuit formation
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