Phenotyping the central nervous system of the embryonic mouse by magnetic resonance microscopy.
Genetic mouse models of neurodevelopmental disorders are being massively generated, but technologies for their high-throughput phenotyping are missing. The potential of high-resolution magnetic resonance imaging (MRI) for structural phenotyping has been demonstrated before. However, application to the embryonic mouse central nervous system has been limited by the insufficient anatomical detail. Here we present a method that combines staining of live embryos with a contrast agent together with MR microscopy after fixation, to provide unprecedented anatomical detail at relevant embryonic stages. By using this method we have phenotyped the embryonic forebrain of Robo1/2(-/-) double mutant mice enabling us to identify most of the well-known anatomical defects in these mutants, as well as novel more subtle alterations. We thus demonstrate the potential of this methodology for a fast and reliable screening of subtle structural abnormalities in the developing mouse brain, as those associated to defects in disease-susceptibility genes of neurologic and psychiatric relevance.
Developmental Neurobiology Unit, Instituto de Neurociencias, Consejo Superior de Investigaciones Científicas & Universidad Miguel Hernández, Sant Joan d'Alacant 03550, Spain.
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Martínez-Martínez
Cellular and Systems Neurobiology Unit, Instituto de Neurociencias, Consejo Superior de Investigaciones Científicas & Universidad Miguel Hernández, Sant Joan d'Alacant 03550, Spain.
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Pacheco-Torres
Developmental Neurobiology Unit, Instituto de Neurociencias, Consejo Superior de Investigaciones Científicas & Universidad Miguel Hernández, Sant Joan d'Alacant 03550, Spain. Electronic address: vborrell@umh.es.
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Borrell
Cellular and Systems Neurobiology Unit, Instituto de Neurociencias, Consejo Superior de Investigaciones Científicas & Universidad Miguel Hernández, Sant Joan d'Alacant 03550, Spain. Electronic address: scanals@umh.es.
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Canals
D000818:Animals; D001921:Brain / Q000196:embryology; D002490:Central Nervous System / Q000196:embryology*; D003287:Contrast Media; D004622:Embryo, Mammalian / Q000033:anatomy & histology*; D047108:Embryonic Development / Q000502:physiology; D005260:Female; D006571:Heterocyclic Compounds; D007091:Image Processing, Computer-Assisted; D007150:Immunohistochemistry; D008279:Magnetic Resonance Imaging / Q000379:methods*; D051379:Mice; D008853:Microscopy; D009942:Organometallic Compounds; D010641:Phenotype; D011247:Pregnancy
D003287:Contrast Media; D006571:Heterocyclic Compounds; D009942:Organometallic Compounds; C050823:gadolinium 1,4,7,10-tetraazacyclododecane-N,N',N'',N'''-tetraacetate
Brain; Development; Embryo; Gadolinium; MRI; Mouse