Transient alterations in granule cell proliferation, apoptosis and migration in postnatal developing cerebellum of CRMP1-/- mice.
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.
Charrier
Emmanuelle
E
INSERM U433, Institut Fédératif des Neurosciences, Université Claude Bernard Lyon 1, Hospices Civils de Lyon, Lyon F-69372, France.
Mosinger
Bedrich
B
Meissirel
Claire
C
Aguera
Michèle
M
Rogemond
Véronique
V
Reibel
Sophie
S
Salin
Paul
P
Chounlamountri
Naura
N
Perrot
Valérie
V
Belin
Marie-Françoise
MF
Goshima
Yoshio
Y
Honnorat
Jérôme
J
Thomasset
Nicole
N
Kolattukudy
Pappachan
P
D000818:Animals; D017209:Apoptosis; D001973:Bromodeoxyuridine / Q000378:metabolism; D002465:Cell Movement / Q000502:physiology*; D049109:Cell Proliferation; D002478:Cells, Cultured; D002531:Cerebellum / Q000166:cytology / Q000254:growth & development*; D003594:Cytoplasmic Granules / Q000502:physiology*; D019084:Fluorescent Antibody Technique, Indirect; D018390:Gene Targeting; D017930:Genes, Reporter; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009419:Nerve Tissue Proteins / Q000172:deficiency / Q000235:genetics* / Q000378:metabolism; D009924:Organ Culture Techniques; D015347:RNA Probes; D000098855:Collapsin Response Mediator Protein 1
D001973:Bromodeoxyuridine; D009419:Nerve Tissue Proteins; D015347:RNA Probes; C502872:Crmp1 protein, mouse; D000098855:Collapsin Response Mediator Protein 1