Neuropilin-2 Is Required In Vivo for Selective Axon Guidance Responses to Secreted Semaphorins

Abstract

Neuropilins are receptors for class 3 secreted semaphorins, most of which can function as potent repulsive axon guidance cues. We have generated mice with a targeted deletion in the neuropilin-2 (Npn-2) locus. Many Npn-2 mutant mice are viable into adulthood, allowing us to assess the role of Npn-2 in axon guidance events throughout neural development. Npn-2 is required for the organization and fasciculation of several cranial nerves and spinal nerves. In addition, several major fiber tracts in the brains of adult mutant mice are either severely disorganized or missing. Our results show that Npn-2 is a selective receptor for class 3 semaphorins in vivo and that Npn-1 and Npn-2 are required for development of an overlapping but distinct set of CNS and PNS projections.

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.…”

“…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.…”

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

“…In vitro studies suggest that all four plexinAs (plexinA1 -A4) form receptor complexes with both neuropilin-1 and neuropilin-2 (Rohm et al, 2000;Suto et al, 2003;Takahashi et al, 1999;Tamagnone et al, 1999). The specific responses of different classes of neurons to individual Sema3s can be explained in part by restricted and unique neuropilin distribution patterns and by the preferential binding of individual Sema3s to neuropilin-1 and/or neuropilin-2 (Chen et al, 1997(Chen et al, , 1998Feiner et al, 1997;Giger et al, 1998Giger et al, , 2000He and Tessier-Lavigne, 1997;Kolodkin et al, 1997). In addition, individual plexinAs also contribute to the specificity of axonal responses to Sema3s (Cheng et al, 2001;Suto et al, 2005;Yaron et al, 2005).…”

“…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).…”

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).…”