title: Profilin1 activity in cerebellar granule neurons is required for radial migration in vivo.
abstract: Neuron migration defects are an important aspect of human neuropathies. The underlying molecular mechanisms of such migration defects are largely unknown. Actin dynamics has been recognized as an important determinant of neuronal migration, and we recently found that the actin-binding protein profilin1 is relevant for radial migration of cerebellar granule neurons (CGN). As the exploited brain-specific mutants lacked profilin1 in both neurons and glial cells, it remained unknown whether profilin1 activity in CGN is relevant for CGN migration in vivo. To test this, we capitalized on a transgenic mouse line that expresses a tamoxifen-inducible Cre variant in CGN, but no other cerebellar cell type. In these profilin1 mutants, the cell density was elevated in the molecular layer, and ectopic CGN occurred. Moreover, 5-bromo-2'-deoxyuridine tracing experiments revealed impaired CGN radial migration. Hence, our data demonstrate the cell autonomous role of profilin1 activity in CGN for radial migration.
authors.affiliation: a Neurobiology/Neurophysiology Group ; University of Kaiserslautern ; Kaiserslautern , Germany.
authors.forename: Jan A
authors.initials: JA
authors.lastname: Kullmann
authors.forename: Ines
authors.initials: I
authors.lastname: Wickertsheim
authors.forename: Lara
authors.initials: L
authors.lastname: Minnerup
authors.forename: Mercedes
authors.initials: M
authors.lastname: Costell
authors.forename: Eckhard
authors.initials: E
authors.lastname: Friauf
authors.forename: Marco B
authors.initials: MB
authors.lastname: Rust
mesh_terms: D000199:Actins / Q000378:metabolism; D000818:Animals; D002465:Cell Movement; D002531:Cerebellum / Q000166:cytology*; D051379:Mice; D008822:Mice, Transgenic; D055495:Neurogenesis; D009457:Neuroglia / Q000166:cytology; D009474:Neurons / Q000166:cytology* / Q000378:metabolism*; D051304:Profilins / Q000378:metabolism*
chemical_list: D000199:Actins; C495739:Pfn1 protein, mouse; D051304:Profilins
keywords: BrdU+, BrdU-positive; BrdU, 5-bromo-2′-deoxyuridine; CGN, cerebellar granule neurons; CaMKIV, Ca2+/calmodulin-dependent protein kinase IV; EGL, external granule cell layer; IGL, internal granule cell layer; ML, molecular layer; Math1-Cre, Math1-mediated Cre expression; NeuN, neuron-specific nuclear protein; P, postnatal day; PI, propidium iodide.; Pfn1, profilin1; actin dynamics; actin treadmilling; actin-binding protein; cerebellar cortex; cerebellar development; cerebellar granule neurons; cerebellum; neuronal migration; profilin; radial migration; βGal+, βGal-positive; βGal, β-galactosidase; βGal−, βGal-negative