Transient alterations in granule cell proliferation, apoptosis and migration in postnatal developing cerebellum of CRMP1^−/– mice

Abstract

Collapsin response mediator proteins (CRMPs) consist of five homologous cytosolic proteins that participate in signal transduction involved in a variety of physiological events. CRMP1 is highly expressed during brain development; however, its functions remains unclear. To gain insight into its function, we generated CRMP1 -/-mice with a knock-in LacZ gene. No gross anatomical changes or behavioral alterations were observed. Expression of CRMP1 was examined by the expression of the knocked-in LacZ gene, in situ hybridization with riboprobes and by imunohistochemistry. CRMP1 was found to be highly expressed in the developing the cerebellum, olfactory bulbs, hypothalamus and retina. In adults, expression level was high in the olfactory bulbs and hippocampus but very low in the retina and cerebellum and undetectable in hypothalamus. To study potential roles of CRMP1, we focused on cerebellum development. CRMP1 -/-mice showed a decrease in the number of granule cells migrating out of explants of developing cerebellum, as did treatment of the explants from normal mice with anti-CRMP1 specific antibodies. CRMP1 -/-mice showed a decrease in granule cell proliferation and apoptosis in external granule cell layers in vivo . Adult cerebellum of CRMP1 -/-did not show any abnormalities.

Collapsin Response Mediator Protein 1 Mediates Reelin Signaling in Cortical Neuronal Migration

“…3D). In adult Reln rl/rl cerebellum, the number of granule cells was reduced, and transient reduction of granule cells was observed in crmp1 Ϫ/Ϫ cerebellum (Rice et al, 1998;Charrier et al, 2006). We found that loss of crmp1 in a dab1 heterozygous background led to the disruption of hippocampal lamination, a Reeler-like phenotype (Fig.…”

“…yotari mice were spontaneous mutants at the dab1 allele (Yoneshima et al, 1997). sema3A and crmp1 mutant mice were generated as described previously (Taniguchi et al, 1997;Charrier et al, 2006). Genotypes of the offspring of all mutant mice were assessed using PCR, as described previously (D'Arcangelo et al, 1997;Kojima et al, 2000;Sasaki et al, 2002;Charrier et al, 2006).…”

“…To elucidate in vivo roles of CRMP1 in the development of the CNS, we have generated crmp1 Ϫ / Ϫ mice (Charrier et al, 2006). We demonstrated that CRMP1 mediates Sema3A signaling in vivo, which is involved in spine maturation (N. Yamashita, A. Morita, Y. Uchida, F. Nakamura, H. Usui, M. Taniguchi, J. Honnorat, P. Kolattukudy, N. Thomasset, K. Takei, T. Takahashi, and Y. Goshima, unpublished observations).…”

Regulation of Spine Development by Semaphorin3A through Cyclin-Dependent Kinase 5 Phosphorylation of Collapsin Response Mediator Protein 1

“…cdk5, sema3A, and crmp1 mutant mice were generated as described previously (Ohshima et al, 1996;Taniguchi et al, 1997;Charrier et al, 2006). Genotypes of the offsprings of all mutant mice were assessed using polymerase chain reaction as described previously (Ohshima et al, 1996;Sasaki et al, 2002;Charrier et al, 2006).…”

CRMP5 (Collapsin Response Mediator Protein 5) Regulates Dendritic Development and Synaptic Plasticity in the Cerebellar Purkinje Cells

“…Unphosphorylated CRMPs bind with tubulin heterodimer, whereas phosphorylation of CRMPs by Rho/ROCK kinase, cyclin-dependent kinase-5 (Cdk5) and glycogen synthase kinase-3␤ (GSK-3␤) lowers the binding affinity of CRMPs to tubulin (Fukata et al, 2002;Uchida et al, 2005). Recently, several knock-out mice studies demonstrated that the loss of CRMPs causes impaired cell migration, dendritic patterning and spine development (Charrier et al, 2006;Yamashita et al, 2006;Su et al, 2007;Yamashita et al, 2007;Quach et al, 2008), suggesting that CRMPs play an important role in the development of nervous system in vivo.…”