β1 integrin maintains integrity of the embryonic neocortical stem cell niche

Karine Loulier, Justin D. Lathia, Veronique Marthiens, Jenne Relucio, Mohamed R. Mughal, Sung Chun Tang, Turhan Coksaygan, Peter E. Hall, Srinivasulu Chigurupati, Bruce Patton, Holly Colognato, Mahendra S. Rao, Mark P. Mattson, Tarik F. Haydar, Charles Ffrench-Constant

Research output: Contribution to journalArticle

114 Citations (Scopus)

Abstract

During embryogenesis, the neural stem cells (NSC) of the developing cerebral cortex are located in the ventricular zone (VZ) lining the cerebral ventricles. They exhibit apical and basal processes that contact the ventricular surface and the pial basement membrane, respectively. This unique architecture is important for VZ physical integrity and fate determination of NSC daughter cells. In addition, the shorter apical process is critical for interkinetic nuclear migration (INM), which enables VZ cell mitoses at the ventricular surface. Despite their importance, the mechanisms required for NSC adhesion to the ventricle are poorly understood. We have shown previously that one class of candidate adhesion molecules, laminins, are present in the ventricular region and that their integrin receptors are expressed by NSC. However, prior studies only demonstrate a role for their interaction in the attachment of the basal process to the overlying pial basement membrane. Here we use antibody-blocking and genetic experiments to reveal an additional and novel requirement for laminin/integrin interactions in apical process adhesion and NSC regulation. Transient abrogation of integrin binding and signalling using blocking antibodies to specifically target the ventricular region in utero results in abnormal INM and alterations in the orientation of NSC divisions. We found that these defects were also observed in laminin a2 deficient mice. More detailed analyses using a multidisciplinary approach to analyse stem cell behaviour by expression of fluorescent transgenes and multiphoton time-lapse imaging revealed that the transient embryonic disruption of laminin/integrin signalling at the VZ surface resulted in apical process detachment from the ventricular surface, dystrophic radial glia fibers, and substantial layering defects in the postnatal neocortex. Collectively, these data reveal novel roles for the laminin/integrin interaction in anchoring embryonic NSCs to the ventricular surface and maintaining the physical integrity of the neocortical niche, with even transient perturbations resulting in long-lasting cortical defects.

Original languageEnglish (US)
Article numbere1000176
JournalPLoS Biology
Volume7
Issue number8
DOIs
StatePublished - Aug 2009

Fingerprint

Stem Cell Niche
Neural Stem Cells
embryonic stem cells
integrins
Embryonic Stem Cells
Stem cells
Integrins
Laminin
stem cells
laminin
niches
Blocking Antibodies
Basement Membrane
basement membrane
Defects
adhesion
Time-Lapse Imaging
Adhesion
Cerebral Ventricles
cerebral ventricles

ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Immunology and Microbiology(all)
  • Neuroscience(all)

Cite this

Loulier, K., Lathia, J. D., Marthiens, V., Relucio, J., Mughal, M. R., Tang, S. C., ... Ffrench-Constant, C. (2009). β1 integrin maintains integrity of the embryonic neocortical stem cell niche. PLoS Biology, 7(8), [e1000176]. https://doi.org/10.1371/journal.pbio.1000176

β1 integrin maintains integrity of the embryonic neocortical stem cell niche. / Loulier, Karine; Lathia, Justin D.; Marthiens, Veronique; Relucio, Jenne; Mughal, Mohamed R.; Tang, Sung Chun; Coksaygan, Turhan; Hall, Peter E.; Chigurupati, Srinivasulu; Patton, Bruce; Colognato, Holly; Rao, Mahendra S.; Mattson, Mark P.; Haydar, Tarik F.; Ffrench-Constant, Charles.

In: PLoS Biology, Vol. 7, No. 8, e1000176, 08.2009.

Research output: Contribution to journalArticle

Loulier, K, Lathia, JD, Marthiens, V, Relucio, J, Mughal, MR, Tang, SC, Coksaygan, T, Hall, PE, Chigurupati, S, Patton, B, Colognato, H, Rao, MS, Mattson, MP, Haydar, TF & Ffrench-Constant, C 2009, 'β1 integrin maintains integrity of the embryonic neocortical stem cell niche', PLoS Biology, vol. 7, no. 8, e1000176. https://doi.org/10.1371/journal.pbio.1000176
Loulier K, Lathia JD, Marthiens V, Relucio J, Mughal MR, Tang SC et al. β1 integrin maintains integrity of the embryonic neocortical stem cell niche. PLoS Biology. 2009 Aug;7(8). e1000176. https://doi.org/10.1371/journal.pbio.1000176
Loulier, Karine ; Lathia, Justin D. ; Marthiens, Veronique ; Relucio, Jenne ; Mughal, Mohamed R. ; Tang, Sung Chun ; Coksaygan, Turhan ; Hall, Peter E. ; Chigurupati, Srinivasulu ; Patton, Bruce ; Colognato, Holly ; Rao, Mahendra S. ; Mattson, Mark P. ; Haydar, Tarik F. ; Ffrench-Constant, Charles. / β1 integrin maintains integrity of the embryonic neocortical stem cell niche. In: PLoS Biology. 2009 ; Vol. 7, No. 8.
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