Fragile X syndrome (FXS) is the most common inherited form of intellectual disability and results from the loss of the fragile X mental retardation protein (FMRP). Many fragile X-related cognitive and behavioral features emerge during childhood and are associated with abnormal synaptic and cellular organization of the cerebral cortex. Identifying the roles of FMRP in cortical development will provide a basis for understanding the pathogenesis of the syndrome. However, how the loss of FMRP influences the developmental trajectory of cortical maturation remains unclear. We took advantage of the stereotyped and well-characterized development of the murine primary somatosensory cortex to examine cortical maturation during a time-window that corresponds to late embryonic and early postnatal development in the human. In the Fmr1 knockout mouse, we find a delay in somatosensory map formation, alterations in the morphology profile of dendrites and spines of layer 4 neurons and a decrease in the synaptic levels of proteins involved in glutamate receptor signaling at times corresponding to the highest levels of FMRP expression. In contrast, cortical arealization, synaptic density in layer 4 and early postnatal regulation of mRNAs encoding synaptic proteins are not altered in Fmr1 knockout mice. The specificity of the developmental delay in Fmr1 knockout mice indicates that the loss of FMRP does not result in a general stalling of cerebral cortex maturation. Instead, our results suggest that inaccurate timing of developmental processes caused by the loss of FMRP may lead to alterations in neural circuitry that underlie behavioral and cognitive dysfunctions associated with FXS.

Till, S., Wijetunge, L., Seidel, V., Harlow, E., Wright, A., Bagni, C., et al. (2012). Altered maturation of the primary somatosensory cortex in a mouse model of fragile X syndrome. HUMAN MOLECULAR GENETICS ONLINE, 21(10), 2143-2156 [10.1093/hmg/dds030].

Altered maturation of the primary somatosensory cortex in a mouse model of fragile X syndrome

BAGNI, CLAUDIA
Membro del Collaboration Group
;
2012-01-01

Abstract

Fragile X syndrome (FXS) is the most common inherited form of intellectual disability and results from the loss of the fragile X mental retardation protein (FMRP). Many fragile X-related cognitive and behavioral features emerge during childhood and are associated with abnormal synaptic and cellular organization of the cerebral cortex. Identifying the roles of FMRP in cortical development will provide a basis for understanding the pathogenesis of the syndrome. However, how the loss of FMRP influences the developmental trajectory of cortical maturation remains unclear. We took advantage of the stereotyped and well-characterized development of the murine primary somatosensory cortex to examine cortical maturation during a time-window that corresponds to late embryonic and early postnatal development in the human. In the Fmr1 knockout mouse, we find a delay in somatosensory map formation, alterations in the morphology profile of dendrites and spines of layer 4 neurons and a decrease in the synaptic levels of proteins involved in glutamate receptor signaling at times corresponding to the highest levels of FMRP expression. In contrast, cortical arealization, synaptic density in layer 4 and early postnatal regulation of mRNAs encoding synaptic proteins are not altered in Fmr1 knockout mice. The specificity of the developmental delay in Fmr1 knockout mice indicates that the loss of FMRP does not result in a general stalling of cerebral cortex maturation. Instead, our results suggest that inaccurate timing of developmental processes caused by the loss of FMRP may lead to alterations in neural circuitry that underlie behavioral and cognitive dysfunctions associated with FXS.
2012
Pubblicato
Rilevanza internazionale
Articolo
Esperti anonimi
Settore BIO/13 - BIOLOGIA APPLICATA
English
Animals; Disease Models, Animal; Fragile X Mental Retardation Protein; Fragile X Syndrome; Mice; Mice, Knockout; Microscopy, Electron; RNA, Messenger; Somatosensory Cortex
Till, S., Wijetunge, L., Seidel, V., Harlow, E., Wright, A., Bagni, C., et al. (2012). Altered maturation of the primary somatosensory cortex in a mouse model of fragile X syndrome. HUMAN MOLECULAR GENETICS ONLINE, 21(10), 2143-2156 [10.1093/hmg/dds030].
Till, S; Wijetunge, L; Seidel, V; Harlow, E; Wright, A; Bagni, C; Contractor, A; Gillingwater, T; Kind, P
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/2108/244903
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