title: Rac1 and Rac3 GTPases regulate the development of hilar mossy cells by affecting the migration of their precursors to the hilus.
abstract: We have previously shown that double deletion of the genes for Rac1 and Rac3 GTPases during neuronal development affects late developmental events that perturb the circuitry of the hippocampus, with ensuing epileptic phenotype. These effects include a defect in mossy cells, the major class of excitatory neurons of the hilus. Here, we have addressed the mechanisms that affect the loss of hilar mossy cells in the dorsal hippocampus of mice depleted of the two Rac GTPases. Quantification showed that the loss of mossy cells was evident already at postnatal day 8, soon after these cells become identifiable by a specific marker in the dorsal hilus. Comparative analysis of the hilar region from control and double mutant mice revealed that synaptogenesis was affected in the double mutants, with strongly reduced presynaptic input from dentate granule cells. We found that apoptosis was equally low in the hippocampus of both control and double knockout mice. Labelling with bromodeoxyuridine at embryonic day 12.5 showed no evident difference in the proliferation of neuronal precursors in the hippocampal primordium, while differences in the number of bromodeoxyuridine-labelled cells in the developing hilus revealed a defect in the migration of immature, developing mossy cells in the brain of double knockout mice. Overall, our data show that Rac1 and Rac3 GTPases participate in the normal development of hilar mossy cells, and indicate that they are involved in the regulation of the migration of the mossy cell precursor by preventing their arrival to the dorsal hilus.
authors.affiliation: Cell Adhesion Unit, Division of Neuroscience, San Raffaele Scientific Institute and San Raffaele University, Milano, Italy.
authors.forename: Roberta
authors.initials: R
authors.lastname: Pennucci
authors.forename: Stefania
authors.initials: S
authors.lastname: Tavano
authors.forename: Diletta
authors.initials: D
authors.lastname: Tonoli
authors.forename: Sara
authors.initials: S
authors.lastname: Gualdoni
authors.forename: Ivan
authors.initials: I
authors.lastname: de Curtis
mesh_terms: D000818:Animals; D001973:Bromodeoxyuridine / Q000378:metabolism; D002452:Cell Count; D016923:Cell Death; D002465:Cell Movement; D049109:Cell Proliferation; D004622:Embryo, Mammalian / Q000166:cytology; D051379:Mice; D018345:Mice, Knockout; D019599:Mossy Fibers, Hippocampal / Q000196:embryology / Q000201:enzymology*; D055495:Neurogenesis; D009479:Neuropeptides / Q000172:deficiency / Q000378:metabolism*; D013234:Stem Cells / Q000166:cytology* / Q000201:enzymology*; D013569:Synapses / Q000378:metabolism; D020744:rac GTP-Binding Proteins / Q000172:deficiency / Q000378:metabolism*; D020830:rac1 GTP-Binding Protein
chemical_list: D009479:Neuropeptides; C484602:Rac1 protein, mouse; C498771:Rac3 protein, mouse; D020744:rac GTP-Binding Proteins; D020830:rac1 GTP-Binding Protein; D001973:Bromodeoxyuridine