Neuropilin-2 is required in vivo for selective axon guidance responses to secreted semaphorins.
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.
Giger
R J
RJ
Department of Neuroscience, The Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA.
Cloutier
J F
JF
Sahay
A
A
Prinjha
R K
RK
Levengood
D V
DV
Moore
S E
SE
Pickering
S
S
Simmons
D
D
Rastan
S
S
Walsh
F S
FS
Kolodkin
A L
AL
Ginty
D D
DD
Geppert
M
M
D000367:Age Factors; D000818:Animals; D001369:Axons / Q000737:chemistry / Q000502:physiology*; D001923:Brain Chemistry / Q000502:physiology; D019556:COS Cells; D002352:Carrier Proteins / Q000378:metabolism*; D017353:Gene Deletion; D018507:Gene Expression Regulation, Developmental; D006023:Glycoproteins / Q000378:metabolism*; D019262:Habenula / Q000737:chemistry / Q000196:embryology / Q000473:pathology; D051379:Mice; D018345:Mice, Knockout; D019599:Mossy Fibers, Hippocampal / Q000737:chemistry / Q000196:embryology / Q000473:pathology; D009046:Motor Neurons / Q000737:chemistry / Q000502:physiology / Q000648:ultrastructure; D009419:Nerve Tissue Proteins / Q000235:genetics* / Q000378:metabolism*; D039942:Neuropilin-1; D017933:Peripheral Nervous System / Q000737:chemistry / Q000196:embryology / Q000473:pathology; D011485:Protein Binding / Q000502:physiology; D051381:Rats; D040121:Semaphorin-3A; D013127:Spinal Nerves / Q000737:chemistry / Q000473:pathology / Q000502:physiology; D017783:Superior Cervical Ganglion / Q000737:chemistry / Q000196:embryology / Q000473:pathology; D013788:Thalamus / Q000737:chemistry / Q000196:embryology / Q000473:pathology; D014321:Trochlear Nerve / Q000737:chemistry / Q000196:embryology / Q000473:pathology
D002352:Carrier Proteins; D006023:Glycoproteins; D009419:Nerve Tissue Proteins; C488217:Sema3a protein, mouse; C488218:Sema3a protein, rat; D040121:Semaphorin-3A; D039942:Neuropilin-1