Arl13b in Primary Cilia Regulates the Migration and Placement of Interneurons in the Developing Cerebral Cortex

Overview

Journal Dev Cell

Publisher Cell Press

Specialties Cell Biology
Reproductive Medicine

Date 2012 Nov 17

PMID 23153492

Citations 134

Authors

Holden Higginbotham

Tae-Yeon Eom

Laura E Mariani

Amelia Bachleda

Joshua Hirt

Vladimir Gukassyan

Corey L Cusack

Cary Lai

Tamara Caspary

E S Anton

Affiliations

Soon will be listed here.

Abstract

Coordinated migration and placement of interneurons and projection neurons lead to functional connectivity in the cerebral cortex; defective neuronal migration and the resultant connectivity changes underlie the cognitive defects in a spectrum of neurological disorders. Here we show that primary cilia play a guiding role in the migration and placement of postmitotic interneurons in the developing cerebral cortex and that this process requires the ciliary protein, Arl13b. Through live imaging of interneuronal cilia, we show that migrating interneurons display highly dynamic primary cilia and we correlate cilia dynamics with the interneuron's migratory state. We demonstrate that the guidance cue receptors essential for interneuronal migration localize to interneuronal primary cilia, but their concentration and dynamics are altered in the absence of Arl13b. Expression of Arl13b variants known to cause Joubert syndrome induce defective interneuronal migration, suggesting that defects in cilia-dependent interneuron migration may in part underlie the neurological defects in Joubert syndrome patients.

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References

Besschetnova T, Kolpakova-Hart E, Guan Y, Zhou J, Olsen B, Shah J . Identification of signaling pathways regulating primary cilium length and flow-mediated adaptation. Curr Biol. 2010; 20(2):182-7. PMC: 2990526. DOI: 10.1016/j.cub.2009.11.072. View

Garcia-Gonzalo F, Corbit K, Sirerol-Piquer M, Ramaswami G, Otto E, Noriega T . A transition zone complex regulates mammalian ciliogenesis and ciliary membrane composition. Nat Genet. 2011; 43(8):776-84. PMC: 3145011. DOI: 10.1038/ng.891. View

Cantagrel V, Silhavy J, Bielas S, Swistun D, Marsh S, Bertrand J . Mutations in the cilia gene ARL13B lead to the classical form of Joubert syndrome. Am J Hum Genet. 2008; 83(2):170-9. PMC: 2495072. DOI: 10.1016/j.ajhg.2008.06.023. View

Wu S, Goebbels S, Nakamura K, Nakamura K, Kometani K, Minato N . Pyramidal neurons of upper cortical layers generated by NEX-positive progenitor cells in the subventricular zone. Proc Natl Acad Sci U S A. 2005; 102(47):17172-7. PMC: 1288007. DOI: 10.1073/pnas.0508560102. View

Manzini M, Walsh C . What disorders of cortical development tell us about the cortex: one plus one does not always make two. Curr Opin Genet Dev. 2011; 21(3):333-9. PMC: 3139684. DOI: 10.1016/j.gde.2011.01.006. View

Arellano J, Guadiana S, Breunig J, Rakic P, Sarkisian M . Development and distribution of neuronal cilia in mouse neocortex. J Comp Neurol. 2011; 520(4):848-73. PMC: 3325766. DOI: 10.1002/cne.22793. View

Yizhar O, Fenno L, Prigge M, Schneider F, Davidson T, OShea D . Neocortical excitation/inhibition balance in information processing and social dysfunction. Nature. 2011; 477(7363):171-8. PMC: 4155501. DOI: 10.1038/nature10360. View

Endoh-Yamagami S, Karkar K, May S, Cobos I, Thwin M, Long J . A mutation in the pericentrin gene causes abnormal interneuron migration to the olfactory bulb in mice. Dev Biol. 2010; 340(1):41-53. DOI: 10.1016/j.ydbio.2010.01.017. View

Louvi A, Grove E . Cilia in the CNS: the quiet organelle claims center stage. Neuron. 2011; 69(6):1046-60. PMC: 3070490. DOI: 10.1016/j.neuron.2011.03.002. View

10.

Wilson S, Wilson J, Wang C, Wang B, McConnell S . Primary cilia and Gli3 activity regulate cerebral cortical size. Dev Neurobiol. 2011; 72(9):1196-212. PMC: 3350755. DOI: 10.1002/dneu.20985. View

11.

Schmid R, McGrath B, Berechid B, Boyles B, Marchionni M, Sestan N . Neuregulin 1-erbB2 signaling is required for the establishment of radial glia and their transformation into astrocytes in cerebral cortex. Proc Natl Acad Sci U S A. 2003; 100(7):4251-6. PMC: 153079. DOI: 10.1073/pnas.0630496100. View

12.

Miyoshi K, Kasahara K, Miyazaki I, Shimizu S, Taniguchi M, Matsuzaki S . Pericentrin, a centrosomal protein related to microcephalic primordial dwarfism, is required for olfactory cilia assembly in mice. FASEB J. 2009; 23(10):3289-97. DOI: 10.1096/fj.08-124420. View

13.

Sawamoto K, Wichterle H, Gonzalez-Perez O, Cholfin J, Yamada M, Spassky N . New neurons follow the flow of cerebrospinal fluid in the adult brain. Science. 2006; 311(5761):629-32. DOI: 10.1126/science.1119133. View

14.

Marin O, Valiente M, Ge X, Tsai L . Guiding neuronal cell migrations. Cold Spring Harb Perspect Biol. 2010; 2(2):a001834. PMC: 2828271. DOI: 10.1101/cshperspect.a001834. View

15.

Kim J, Lee J, Heynen-Genel S, Suyama E, Ono K, Lee K . Functional genomic screen for modulators of ciliogenesis and cilium length. Nature. 2010; 464(7291):1048-51. PMC: 2929961. DOI: 10.1038/nature08895. View

16.

Xu Q, Tam M, Anderson S . Fate mapping Nkx2.1-lineage cells in the mouse telencephalon. J Comp Neurol. 2007; 506(1):16-29. DOI: 10.1002/cne.21529. View

17.

Berbari N, OConnor A, Haycraft C, Yoder B . The primary cilium as a complex signaling center. Curr Biol. 2009; 19(13):R526-35. PMC: 2814769. DOI: 10.1016/j.cub.2009.05.025. View

18.

Breunig J, Sarkisian M, Arellano J, Morozov Y, Ayoub A, Sojitra S . Primary cilia regulate hippocampal neurogenesis by mediating sonic hedgehog signaling. Proc Natl Acad Sci U S A. 2008; 105(35):13127-32. PMC: 2529104. DOI: 10.1073/pnas.0804558105. View

19.

Poretti A, Boltshauser E, Loenneker T, Valente E, Brancati F, Ilyasov K . Diffusion tensor imaging in Joubert syndrome. AJNR Am J Neuroradiol. 2007; 28(10):1929-33. PMC: 8134246. DOI: 10.3174/ajnr.A0703. View

20.

Higginbotham H, Gleeson J . The centrosome in neuronal development. Trends Neurosci. 2007; 30(6):276-83. DOI: 10.1016/j.tins.2007.04.001. View