Essential role of Rac1 and Rac3 GTPases in neuronal development

Sara Corbetta, Sara Gualdoni, Gabriele Ciceri, Marta Monari, Emanuela Zuccaro, Victor L J Tybulewicz, Ivan De Curtis

Research output: Contribution to journalArticle

Abstract

Rac GTPases are members of the Rho family regulating the actin cytoskeleton and implicated in neuronal development. Ubiquitous Rac1 and neuron-specific Rac3 GTPases are coexpressed in the developing mammalian brain. We used Cre-mediated conditional deletion of Rac1 in neurons combined with knockout of neuron-specific Rac3 to study the role of these GTPases in neural development. We found that lack of both genes causes motor behavioral defects, epilepsy, and premature death of mice. Deletion of either GTPase does not produce evident phenotypes. Double-knockout mice show specific defects in the development of the hippocampus. Selective impairment of the dorsal hilus of double-knockout animals is associated with alteration in the formation of the hippocampal circuitry. Axonal pathways to and from the dorsal hilus are affected because of the deficit of hilar mossy cells. Moreover, analysis of Rac function in hippocampal cultures shows that spine formation is strongly hampered only in neurons lacking both Rac proteins. These findings show for the first time that both Rac1 and Rac3 are important for the development of the nervous system, wherein they play complementary roles during late stages of neuronal and brain development.

Original languageEnglish
Pages (from-to)1347-1357
Number of pages11
JournalFASEB Journal
Volume23
Issue number5
DOIs
Publication statusPublished - May 2009

Fingerprint

GTP Phosphohydrolases
Neurons
Hippocampus
Brain
rac GTP-Binding Proteins
rho GTP-Binding Proteins
Defects
Premature Mortality
Neurology
Actin Cytoskeleton
Knockout Mice
Nervous System
Actins
Epilepsy
Animals
Spine
Genes
Phenotype

Keywords

  • Axons
  • Dendritic spines
  • Hilar mossy cells
  • Hippocampus

ASJC Scopus subject areas

  • Biochemistry
  • Biotechnology
  • Genetics
  • Molecular Biology

Cite this

Corbetta, S., Gualdoni, S., Ciceri, G., Monari, M., Zuccaro, E., Tybulewicz, V. L. J., & De Curtis, I. (2009). Essential role of Rac1 and Rac3 GTPases in neuronal development. FASEB Journal, 23(5), 1347-1357. https://doi.org/10.1096/fj.08-121574

Essential role of Rac1 and Rac3 GTPases in neuronal development. / Corbetta, Sara; Gualdoni, Sara; Ciceri, Gabriele; Monari, Marta; Zuccaro, Emanuela; Tybulewicz, Victor L J; De Curtis, Ivan.

In: FASEB Journal, Vol. 23, No. 5, 05.2009, p. 1347-1357.

Research output: Contribution to journalArticle

Corbetta, S, Gualdoni, S, Ciceri, G, Monari, M, Zuccaro, E, Tybulewicz, VLJ & De Curtis, I 2009, 'Essential role of Rac1 and Rac3 GTPases in neuronal development', FASEB Journal, vol. 23, no. 5, pp. 1347-1357. https://doi.org/10.1096/fj.08-121574
Corbetta S, Gualdoni S, Ciceri G, Monari M, Zuccaro E, Tybulewicz VLJ et al. Essential role of Rac1 and Rac3 GTPases in neuronal development. FASEB Journal. 2009 May;23(5):1347-1357. https://doi.org/10.1096/fj.08-121574
Corbetta, Sara ; Gualdoni, Sara ; Ciceri, Gabriele ; Monari, Marta ; Zuccaro, Emanuela ; Tybulewicz, Victor L J ; De Curtis, Ivan. / Essential role of Rac1 and Rac3 GTPases in neuronal development. In: FASEB Journal. 2009 ; Vol. 23, No. 5. pp. 1347-1357.
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