title: Bacurd2 is a novel interacting partner to Rnd2 which controls radial migration within the developing mammalian cerebral cortex.
abstract: BACKGROUND
  During fetal brain development in mammals, newborn neurons undergo cell migration to reach their appropriate positions and form functional circuits. We previously reported that the atypical RhoA GTPase Rnd2 promotes the radial migration of mouse cerebral cortical neurons (Nature 455(7209):114-8, 2008; Neuron 69(6):1069-84, 2011), but its downstream signalling pathway is not well understood.
  
  
  RESULTS
  We have identified BTB-domain containing adaptor for Cul3-mediated RhoA degradation 2 (Bacurd2) as a novel interacting partner to Rnd2, which promotes radial migration within the developing cerebral cortex. We find that Bacurd2 binds Rnd2 at its C-terminus, and this interaction is critical to its cell migration function. We show that forced expression or knockdown of Bacurd2 impairs neuronal migration within the embryonic cortex and alters the morphology of immature neurons. Our in vivo cellular analysis reveals that Bacurd2 influences the multipolar-to-bipolar transition of radially migrating neurons in a cell autonomous fashion. When we addressed the potential signalling relationship between Bacurd2 and Rnd2 using a Bacurd2-Rnd2 chimeric construct, our results suggest that Bacurd2 and Rnd2 could interact to promote radial migration within the embryonic cortex.
  
  
  CONCLUSIONS
  Our studies demonstrate that Bacurd2 is a novel player in neuronal development and influences radial migration within the embryonic cerebral cortex.
authors.affiliation: EMBL Australia, The Australian Regenerative Medicine Institute, Monash University, Clayton, Victoria, 3800, Australia. ivan.gladwyn-ng@monash.edu.
authors.forename: Ivan Enghian
authors.initials: IE
authors.lastname: Gladwyn-Ng
authors.affiliation: EMBL Australia, The Australian Regenerative Medicine Institute, Monash University, Clayton, Victoria, 3800, Australia. shanshan.li@hotmail.com.
authors.forename: Shan Shan
authors.initials: SS
authors.lastname: Li
authors.affiliation: EMBL Australia, The Australian Regenerative Medicine Institute, Monash University, Clayton, Victoria, 3800, Australia. zhengdong.qu@monash.edu.
authors.forename: Zhengdong
authors.initials: Z
authors.lastname: Qu
authors.affiliation: EMBL Australia, The Australian Regenerative Medicine Institute, Monash University, Clayton, Victoria, 3800, Australia. jmdavis@student.unimelb.edu.au.
authors.forename: John Michael
authors.initials: JM
authors.lastname: Davis
authors.affiliation: EMBL Australia, The Australian Regenerative Medicine Institute, Monash University, Clayton, Victoria, 3800, Australia. linh.ngo@monash.edu.|The Harry Perkins Institute of Medical Research, Perth, Australia. linh.ngo@monash.edu.
authors.forename: Linh
authors.initials: L
authors.lastname: Ngo
authors.affiliation: EMBL Australia, The Australian Regenerative Medicine Institute, Monash University, Clayton, Victoria, 3800, Australia. matilda.haas@monash.edu.
authors.forename: Matilda
authors.initials: M
authors.lastname: Haas
authors.affiliation: Department of Biology, Portland State University, Portland, Oregon, 96207, USA. jsinger@pdx.edu.
authors.forename: Jeffrey
authors.initials: J
authors.lastname: Singer
authors.affiliation: EMBL Australia, The Australian Regenerative Medicine Institute, Monash University, Clayton, Victoria, 3800, Australia. julian.heng@perkins.uwa.edu.au.|The Harry Perkins Institute of Medical Research, Perth, Australia. julian.heng@perkins.uwa.edu.au.|Centre for Medical Research, The University of Western Australia, Perth, Australia. julian.heng@perkins.uwa.edu.au.|Present address: The Harry Perkins Institute of Medical Research, Perth, Australia. julian.heng@perkins.uwa.edu.au.
authors.forename: Julian Ik-Tsen
authors.initials: JI
authors.lastname: Heng
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics / Q000378:metabolism; D000595:Amino Acid Sequence; D000818:Animals; D001665:Binding Sites; D002465:Cell Movement; D002540:Cerebral Cortex / Q000166:cytology / Q000196:embryology*; D005822:Genetic Vectors / Q000235:genetics; D057809:HEK293 Cells; D006801:Humans; D051379:Mice; D008969:Molecular Sequence Data; D016297:Mutagenesis, Site-Directed; D009415:Nerve Net / Q000196:embryology*; D011485:Protein Binding; D025941:Protein Interaction Mapping; D017434:Protein Structure, Tertiary; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000494:pharmacology; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D015398:Signal Transduction; D014162:Transfection; D020798:Two-Hybrid System Techniques; D020741:rho GTP-Binding Proteins / Q000502:physiology*
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D034741:RNA, Small Interfering; D011993:Recombinant Fusion Proteins; C115968:TNFAIP1 protein, human; C475019:Rnd2 protein, mouse; D020741:rho GTP-Binding Proteins