title: Ndfip1 expression in developing neurons indicates a role for protein ubiquitination by Nedd4 E3 ligases during cortical development.
abstract: During development, protein substrates need to be removed and degraded when they are no longer required. The E3 ubiquitin ligases, including Nedd4 family proteins, are a major group of enzymes responsible for adding ubiquitin chains to protein substrates prior to their degradation. Ndfip1 (Nedd4 family-interacting protein 1) is an adaptor and activator for Nedd4-family ubiquitin ligases for increasing substrate specificity. To study Nedd4-mediated ubiquitination during cortical development, we have mapped the spatio-temporal dynamics of Ndfip1 protein expression by immunocytochemistry. Ndfip1 expression was observed from embryonic day 11 (E11.5) until adult stages. Its presence increased during the postnatal stages and peaked at postnatal day 7 (P7). Spatially, Ndfip1 was found in the ventricular and marginal zones during corticogenesis but also in the cortical plate and subplate during midstage cortical development (E15.5). Postnatally, Ndfip1 was expressed in all cortical neurons (but not in glial cells) and this expression was both ubiquitous and uniform across cortical layers involving both pyramidal and non-pyramidal neurons. This consistent but dynamic pattern of Ndfip1 expression in temporal and spatial domains of the cortical landscape is indicative of complex programs of protein ubiquitination during corticogenesis.
authors.affiliation: Brain Development and Regeneration Laboratory, The Florey Institute of Neuroscience and Mental Health, University of Melbourne, Parkville 3010, Australia.
authors.forename: Choo-Peng
authors.initials: CP
authors.lastname: Goh
authors.forename: Ley-Hian
authors.initials: LH
authors.lastname: Low
authors.forename: Ulrich
authors.initials: U
authors.lastname: Putz
authors.forename: Jenny
authors.initials: J
authors.lastname: Gunnersen
authors.forename: Vicki
authors.initials: V
authors.lastname: Hammond
authors.forename: Jason
authors.initials: J
authors.lastname: Howitt
authors.forename: Seong-Seng
authors.initials: SS
authors.lastname: Tan
mesh_terms: D000818:Animals; D002352:Carrier Proteins / Q000378:metabolism*; D002540:Cerebral Cortex / Q000196:embryology / Q000254:growth & development / Q000378:metabolism*; D056827:Endosomal Sorting Complexes Required for Transport / Q000378:metabolism*; D018507:Gene Expression Regulation, Developmental; D036341:Intercellular Signaling Peptides and Proteins; D007395:Interneurons / Q000378:metabolism; D008565:Membrane Proteins / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D009024:Morphogenesis; D000075702:Nedd4 Ubiquitin Protein Ligases; D009474:Neurons / Q000378:metabolism*; D017966:Pyramidal Cells / Q000378:metabolism; D044767:Ubiquitin-Protein Ligases / Q000378:metabolism*; D054875:Ubiquitination
chemical_list: D002352:Carrier Proteins; D056827:Endosomal Sorting Complexes Required for Transport; D036341:Intercellular Signaling Peptides and Proteins; D008565:Membrane Proteins; C499188:Ndfip1 protein, mouse; D000075702:Nedd4 Ubiquitin Protein Ligases; C000618461:Nedd4l protein, mouse; D044767:Ubiquitin-Protein Ligases
keywords: Cerebral cortex; Comm; Cortical development; Ndfip1; Nedd4; Nedd4 family-interacting protein 1; PTEN; Protein expression; Robo; commissureless; neural precursor cell-expressed developmentally down-regulated gene 4; phosphatase and tensin homolog deleted chromosome 10; roundabout