RESUMEN
Presenilin-1 (PS1) is a transmembrane protein that is in many cases responsible for the development of familial Alzheimer's disease. PS1 is widely expressed in embryogenesis and is essential for neurogenesis, somitogenesis, angiogenesis, and cardiac morphogenesis. To further investigate the role of PS1 in the brain, we inactivated the PS1 gene in Wnt1 cell lineages using the Cre-loxP recombination system. Here we show that conditional inactivation of PS1 in Wnt1 cell lineages results in congenital hydrocephalus and subcommissural organ abnormalities, suggesting a possible role of PS1 in the regulation of cerebrospinal fluid homeostasis.
Asunto(s)
Predisposición Genética a la Enfermedad/genética , Hidrocefalia/genética , Malformaciones del Sistema Nervioso/genética , Presenilina-1/genética , Órgano Subcomisural/anomalías , Proteína Wnt1/genética , Animales , Linaje de la Célula/genética , Ventrículos Cerebrales/anomalías , Ventrículos Cerebrales/patología , Líquido Cefalorraquídeo/fisiología , Presión del Líquido Cefalorraquídeo/fisiología , Modelos Animales de Enfermedad , Homeostasis/genética , Hidrocefalia/patología , Hidrocefalia/fisiopatología , Ratones , Ratones Noqueados , Ratones Transgénicos , Malformaciones del Sistema Nervioso/metabolismo , Malformaciones del Sistema Nervioso/patología , Presenilina-1/antagonistas & inhibidores , Presenilina-1/deficiencia , Órgano Subcomisural/fisiopatologíaRESUMEN
The heterogeneous nature of congenital hydrocephalus has hampered our understanding of the molecular basis of this common clinical problem. However, disease gene identification and characterization of multiple transgenic mouse models has highlighted the importance of the subcommissural organ (SCO) and the ventricular ependymal (vel) cells. Here, we review how altered development and function of the SCO and vel cells contributes to hydrocephalus.
Asunto(s)
Hidrocefalia/líquido cefalorraquídeo , Hidrocefalia/etiología , Órgano Subcomisural/fisiopatología , Animales , Moléculas de Adhesión Celular , Cilios/fisiología , Homeostasis/fisiología , Humanos , Ratones , Transducción de Señal/fisiologíaRESUMEN
The structure of the human subcommissuralorgan during its ontogenic development in 24human embryos and foetuses ranging from 6 to40 weeks of gestation (WG), and three adulthuman brains from 27-, 65- and 70-year old subjectswas investigated using both qualitative andquantitative methods. Concurrently, the appearanceof the subcommissural organ, pineal glandand mesocoelic recess was determined by studyingtheir structure, length and volume. Thehuman SCO appears at the beginning of 8th WG,which confirms previous results; the completematuration of the SCO occurs at the 15th WG andthe following three parts can be distinguished:the precommissural part, located in the rostralzone of the posterior commissure (PC) andextending to the pineal recess; the subcommissuralpart, located under the PC, and the retrocommissuralpart, located in the caudal zone ofthe PC, in the mesocoelic recess and at thebeginning of the Sylvian aqueduct. The reductionin size of the SCO begins after the 17th WGand this decrease in size begins in the precommissural,continues in the subcommissural, andfinishes in the retrocommissural part. The regressionand atrophies of the SCO begin after birth,and the SCO disappears completely after the ageof 30. The mesocoelic recess starts to form at thebeginning of the 10th WG, and is completely formedby the 14th WG and this is where the retrocommissuralpart of the SCO is located. In the 40th WG the regression of the mesocoelic recessbegins and this takes place at the same time asthe regression of the SCO. A parallel developmentbetween the SCO and the pineal wasfound. Thus, we observed the first appearance ofthe pineal recess in the 7-8th WG; during the 10thWG a compact mass of cells appeared in the rostralpart of pineal recess and by the 15th WG thepineal gland (PG) had acquired an almost definitiveaspect
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