Gladwyn-Ng et al (Neural Dev 2015) Bacurd2 is a novel interacting partner to Rnd2 which controls radial migration within the developing mammalian cerebral cortex.pdf
Adaptor Proteins, Signal Transducing/genetics/metabolism; Amino Acid Sequence; Animals; Binding Sites; Cell Movement; Cerebral Cortex/cytology/embryology; Genetic Vectors/genetics; HEK293 Cells; Humans; Mice; Molecular Sequence Data; Mutagenesis, Site-Directed; Nerve Net/embryology; Protein Binding; Protein Interaction Mapping; Protein Structure, Tertiary; RNA Interference; RNA, Small Interfering/pharmacology; Recombinant Fusion Proteins/metabolism; Signal Transduction; Transfection; Two-Hybrid System Techniques; rho GTP-Binding Proteins/physiology
Abstract :
[en] 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.
Disciplines :
Life sciences: Multidisciplinary, general & others
Gupta A, Tsai LH, Wynshaw-Boris A. Life is a journey: a genetic look at neocortical development. Nat Rev Genet. 2002;3(5):342-55.
Marin O, Rubenstein JL. A long, remarkable journey: tangential migration in the telencephalon. Nat Rev Neurosci. 2001;2(11):780-90.
Marin O, Rubenstein JL. Cell migration in the forebrain. Annu Rev Neurosci. 2003;26:441-83. doi:10.1146/annurev.neuro.26.041002.131058041002.131058.
Heng JI, Chariot A, Nguyen L. Molecular layers underlying cytoskeletal remodelling during cortical development. Trends Neurosci. 2010;33(1):38-47. doi:10.1016/j.tins.2009.09.003.
Leventer RJ, Guerrini R, Dobyns WB. Malformations of cortical development and epilepsy. Dialogues Clin Neurosci. 2008;10(1):47-62.
Heng JI, Nguyen L, Castro DS, Zimmer C, Wildner H, Armant O, et al. Neurogenin 2 controls cortical neuron migration through regulation of Rnd2. Nature. 2008;455(7209):114-8. doi:10.1038/nature07198.
Pacary E, Heng J, Azzarelli R, Riou P, Castro D, Lebel-Potter M, et al. Proneural transcription factors regulate different steps of cortical neuron migration through Rnd-mediated inhibition of RhoA signaling. Neuron. 2011;69(6):1069-84. doi:S0896-6273(11)00116-4 10.1016/j.neuron.2011.02.018.
Heng J, Guillemot F. Proneural proteins and the development of the cerebral cortex. In: Kageyama R, editor. Cortical Development: Neural Diversity and Neocortical Organization. Springer Global; 2013. p. In press.
Alfano C, Viola L, Heng JI, Pirozzi M, Clarkson M, Flore G, et al. COUP-TFI promotes radial migration and proper morphology of callosal projection neurons by repressing Rnd2 expression. Development. 2011;138(21):4685-97. doi:dev.068031 10.1242/dev.068031.
Heng JI, Qu Z, Ohtaka-Maruyama C, Okado H, Kasai M, Castro D et al. The zinc finger transcription factor RP58 negatively regulates Rnd2 for the control of neuronal migration during cortical development. Cereb Cortex. 2013. doi:bht277 10.1093/cercor/bht277
Ohtaka-Maruyama C, Hirai S, Miwa A, Heng JI, Shitara H, Ishii R, et al. RP58 regulates the multipolar-bipolar transition of newborn neurons in the developing cerebral cortex. Cell Rep. 2013;3(2):458-71. doi:S2211-1247(13)00019-3 10.1016/j.celrep.2013.01.012.
Pacary E, Azzarelli R, Guillemot F. Rnd3 coordinates early steps of cortical neurogenesis through actin-dependent and -independent mechanisms. Nat Commun. 2013;4:1635. doi:ncomms2614 10.1038/ncomms2614.
Chardin P. Function and regulation of Rnd proteins. Nat Rev Mol Cell Biol. 2006;7(1):54-62. doi:nrm1788 10.1038/nrm1788.
Riou P, Villalonga P, Ridley AJ. Rnd proteins: multifunctional regulators of the cytoskeleton and cell cycle progression. Bioessays. 2010;32(11):986-92. doi:10.1002/bies.201000060.
Heng JI, Tan SS. Cloning and characterization of GRIPE, a novel interacting partner of the transcription factor E12 in developing mouse forebrain. J Biol Chem. 2002;277(45):43152-9. doi:10.1074/jbc.M204858200 M204858200.
LoTurco JJ, Bai J. The multipolar stage and disruptions in neuronal migration. Trends Neurosci. 2006;29(7):407-13. doi:S0166-2236(06)00094-4 10.1016/j.tins.2006.05.006.
Noctor SC, Martinez-Cerdeno V, Ivic L, Kriegstein AR. Cortical neurons arise in symmetric and asymmetric division zones and migrate through specific phases. Nat Neurosci. 2004;7(2):136-44. doi:10.1038/nn1172 nn1172.
Chen Y, Yang Z, Meng M, Zhao Y, Dong N, Yan H, et al. Cullin mediates degradation of RhoA through evolutionarily conserved BTB adaptors to control actin cytoskeleton structure and cell movement. Mol Cell. 2009;6:841-55. doi:S1097-2765(09)00632-7 10.1016/j.molcel.2009.09.004.
Nguyen L, Besson A, Heng JI, Schuurmans C, Teboul L, Parras C, et al. p27kip1 independently promotes neuronal differentiation and migration in the cerebral cortex. Genes Dev. 2006;20(11):1511-24. doi:gad.377106 10.1101/gad.377106.
Riou P, Kjaer S, Garg R, Purkiss A, George R, Cain RJ, et al. 14-3-3 proteins interact with a hybrid prenyl-phosphorylation motif to inhibit G proteins. Cell. 2013;153(3):640-53. doi: 10.1016/j.cell.2013.03.044.
Azzarelli R, Pacary E, Garg R, Garcez P, van den Berg D, Riou P, et al. An antagonistic interaction between PlexinB2 and Rnd3 controls RhoA activity and cortical neuron migration. Nat Commun. 2014;5:3405. doi:10.1038/ncomms4405.
Golzio C, Willer J, Talkowski ME, Oh EC, Taniguchi Y, Jacquemont S, et al. KCTD13 is a major driver of mirrored neuroanatomical phenotypes of the 16p11.2 copy number variant. Nature. 2012;485(7398):363-7. doi:nature11091 10.1038/nature11091.
Breuss M, Heng JI, Poirier K, Tian G, Jaglin XH, Qu Z, et al. Mutations in the beta-tubulin gene TUBB5 cause microcephaly with structural brain abnormalities. Cell Rep. 2012;62(6):1554. doi:S2211-1247(12)00414-7 10.1016/j.celrep.2012.11.017.
