Disruption of Semaphorin III/D Gene Causes Severe Abnormality in Peripheral Nerve Projection

Abstract

The molecules of the collapsin/semaphorin gene family have been thought to play an essential role in axon guidance during development. Semaphorin III/D is a member of this family, has been shown to repel dorsal root ganglion (DRG) axons in vitro, and has been implicated in the patterning of sensory afferents in the spinal cord. Although semaphorin III/D mRNA is expressed in a wide variety of neural and nonneural tissues in vivo, the role played by semaphorin III/D in regions other than the spinal cord is not known. Here, we show that mice homozygous for a targeted mutation in semaphorin III/D show severe abnormality in peripheral nerve projection. This abnormality is seen in the trigeminal, facial, vagus, accessory, and glossopharyngeal nerves but not in the oculomotor nerve. These results suggest that semaphorin III/D functions as a selective repellent in vivo.

Expression of multiple class three semaphorins in the retina and along the path of zebrafish retinal axons

“…The expression of sema3s in the zebrafish retina appears to differ from that reported in other species. For instance, while sema3Aa is expressed in a select population of cells in the INL of the zebrafish retina well after the optic projection has formed, in both the chick and mouse retinas Sema3A is found throughout the embryonic eye (Taniguchi et al, 1997;Chilton and Guthrie, 2003). Moreover, we found no sema3E label in the zebrafish retina, but sema3E is expressed in the outer layers of the embryonic mouse retina (Steinbach et al, 2002).…”

“…For example, in Sema3A null mice sensory axons grow aberrantly into regions of the spinal cord that normally express Sema3A and neuronal processes of pyramidal neurons are oriented randomly rather than towards the brain surface (Behar et al, 1996). There are also severe defects in cranial nerve axon fasciculation in these mice (Taniguchi et al, 1997;Catalano et al, 1998). Furthermore, perturbation of Sema3Aa signalling in zebrafish causes the axons of ventral spinal motoneurons, which normally grow along the medial portion of the somite, to extend aberrantly into anterior or posterior regions (Shoji et al, 1998;Sato-Maeda et al, 2006).…”

ADAM metalloproteases promote a developmental switch in responsiveness to the axonal repellant Sema3A

“…Finally, we examined whether axons that exhibit pathfinding errors in embryos with defective Sema3A signalling (namely the ARTICLE Sema3A, Nrp1 and Plexin-A mutants 25,29,55,56 ) also misproject in ADAM10/17 double-knockout embryos. Contrary to the former mutants, whose axons extend beyond their normal targets due to lack of Sema3A inhibitory signalling, axonal projections of the ADAM knockouts are expected to be more restricted than wild type due to increased sensitivity to the repellant.…”

Turning heads: Development of vertebrate branchiomotor neurons

“…In mouse, a Sema3A receptor gene, Neuropilin2, is expressed in BMNs (Chen et al, 2000), whereas Sema3A is expressed in the first and second branchial arches . The nV and nVII cranial nerves (containing nV and nVII BMN axons, respectively) are slightly defasciculated in Neuropilin2 knockout mice (Chen et al, 2000;Giger et al, 2000) and more severely defasciculated in Neuropilin1 and Sema3A knockout mice (Kitsukawa et al, 1997;Taniguchi et al, 1997). These data suggest strongly that Semaphorin-mediated repulsive interactions channel the extension of BMN axons into the branchial arch mesenchyme but are likely not involved in guiding axons of different BMN subtypes to specific arch targets.…”