Neuropilin-2 Regulates the Development of Select Cranial and Sensory Nerves and Hippocampal Mossy Fiber Projections

Abstract

Neuropilin-1 and neuropilin-2 bind differentially to different class 3 semaphorins and are thought to provide the ligand-binding moieties in receptor complexes mediating repulsive responses to these semaphorins. Here, we have studied the function of neuropilin-2 through analysis of a neuropilin-2 mutant mouse, which is viable and fertile. Repulsive responses of sympathetic and hippocampal neurons to Sema3F but not to Sema3A are abolished in the mutant. Marked defects are observed in the development of several cranial nerves, in the initial central projections of spinal sensory axons, and in the anterior commissure, habenulo-interpeduncular tract, and the projections of hippocampal mossyfiber axons in the infrapyramidal bundle. Our results show that neuropilin-2 is an essential component of the Sema3F receptor and identify key roles for neuropilin-2 in axon guidance in the PNS and CNS.

MICAL flavoprotein monooxygenases: Expression during neural development and following spinal cord injuries in the rat

“…The idea that semaphorins regulate aspects of postnatal and adult neuronal plasticity is supported by several observations. First, mice deficient for Sema3F, neuropilin-2, or plexinA3 show defects in axonal pruning of postnatal hippocampal projections (Bagri et al, 2003;Chen et al, 2000Chen et al, , 2001Giger et al, 2000;Sahay et al, 2003). Second, Sema3s act as modulators of synaptic transmission in postnatal hippocampal slice cultures (Sahay et al, 2005).…”

Turning heads: Development of vertebrate branchiomotor neurons

“…BMN axon outgrowth from rat hindbrain explants is reduced in the presence of Sem D (Sema3A) (Varela-Echavarria et al, 1997). Of interest, BMN axons exit normally from the hindbrain in mice defective for Neuropilin2, a Sema3A receptor that is expressed in BMN nuclei (Chen et al, , 2000Giger et al, 2000), and in mice defective for Sema3A, which is expressed in the ventral hindbrain Varela-Echavarria et al, 1997;Catalano et al, 1998). However, because BMN axon outgrowth within the hindbrain was not specifically examined in the mutant embryos, defects in axon outgrowth at the ventral midline, and a specific role for semaphorins in this process, cannot be ruled out.…”

“…Furthermore, when sema4E is ubiquitously expressed in the embryo, BMN axon outgrowth into the branchial arches is specifically eliminated, indicating that Sema4E may play a significant role in the guidance of all BMN axons (Xiao et al, 2003). 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).…”

“…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.…”

Cranial expression of class 3 secreted semaphorins and their neuropilin receptors

“…NPN2 null mice also exhibit defective cranial axon projections, most notably dramatic defasciculation of the oculomotor nerve and an apparent absence of the trochlear nerve, even though the cell bodies are intact. The trigeminal and facial nerves are also defasciculated at their distal ends (Chen et al, 2000;Giger et al, 2000).…”