title: Cranial nerve fasciculation and Schwann cell migration are impaired after loss of Npn-1.
abstract: Interaction of the axon guidance receptor Neuropilin-1 (Npn-1) with its repulsive ligand Semaphorin 3A (Sema3A) is crucial for guidance decisions, fasciculation, timing of growth and axon-axon interactions of sensory and motor projections in the embryonic limb. At cranial levels, Npn-1 is expressed in motor neurons and sensory ganglia and loss of Sema3A-Npn-1 signaling leads to defasciculation of the superficial projections to the head and neck. The molecular mechanisms that govern the initial fasciculation and growth of the purely motor projections of the hypoglossal and abducens nerves in general, and the role of Npn-1 during these events in particular are, however, not well understood. We show here that selective removal of Npn-1 from somatic motor neurons impairs initial fasciculation and assembly of hypoglossal rootlets and leads to reduced numbers of abducens and hypoglossal fibers. Ablation of Npn-1 specifically from cranial neural crest and placodally derived sensory tissues recapitulates the distal defasciculation of mixed sensory-motor nerves of trigeminal, facial, glossopharyngeal and vagal projections, which was observed in Npn-1(-/-) and Npn-1(Sema-) mutants. Surprisingly, the assembly and fasciculation of the purely motor hypoglossal nerve are also impaired and the number of Schwann cells migrating along the defasciculated axonal projections is reduced. These findings are corroborated by partial genetic elimination of cranial neural crest and embryonic placodes, where loss of Schwann cell precursors leads to aberrant growth patterns of the hypoglossal nerve. Interestingly, rostral turning of hypoglossal axons is not perturbed in any of the investigated genotypes. Thus, initial hypoglossal nerve assembly and fasciculation, but not later guidance decisions depend on Npn-1 expression and axon-Schwann cell interactions.
authors.affiliation: Institute of Developmental Genetics, Helmholtz Zentrum München, German Research Center for Environmental Health, Neuherberg.
authors.forename: Rosa-Eva
authors.initials: RE
authors.lastname: Huettl
authors.forename: Andrea B
authors.initials: AB
authors.lastname: Huber
mesh_terms: D000010:Abducens Nerve / Q000196:embryology / Q000378:metabolism; D000818:Animals; D001369:Axons / Q000378:metabolism; D002465:Cell Movement; D003391:Cranial Nerves / Q000196:embryology / Q000378:metabolism*; D004622:Embryo, Mammalian / Q000196:embryology / Q000378:metabolism; D005207:Fasciculation / Q000235:genetics / Q000378:metabolism*; D005260:Female; D007002:Hypoglossal Nerve / Q000196:embryology / Q000378:metabolism; D007150:Immunohistochemistry; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D009046:Motor Neurons / Q000378:metabolism; D009154:Mutation; D009432:Neural Crest / Q000196:embryology / Q000378:metabolism; D039942:Neuropilin-1 / Q000235:genetics / Q000378:metabolism*; D055757:SOXE Transcription Factors / Q000378:metabolism; D012583:Schwann Cells / Q000378:metabolism*; D040121:Semaphorin-3A / Q000235:genetics / Q000378:metabolism; D011984:Sensory Receptor Cells / Q000378:metabolism; D015398:Signal Transduction
chemical_list: D055757:SOXE Transcription Factors; D040121:Semaphorin-3A; C527924:Sox10 protein, mouse; D039942:Neuropilin-1