RESUMEN
The development of the cerebral cortex requires the coordination of multiple processes ranging from the proliferation of progenitors to the migration and establishment of connectivity of the newborn neurons. Epigenetic regulation carried out by the COREST/LSD1 complex has been identified as a mechanism that regulates the development of pyramidal neurons of the cerebral cortex. We now identify the association of the multifunctional RNA-binding protein SFPQ to LSD1 during the development of the cerebral cortex. In vivo reduction of SFPQ dosage by in utero electroporation of a shRNA results in impaired radial migration of newborn pyramidal neurons, in a similar way to that observed when COREST or LSD1 expressions are decreased. Diminished SFPQ expression also associates to decreased proliferation of progenitor cells, while it does not affect the acquisition of neuronal fate. These results are compatible with the idea that SFPQ, plays an important role regulating proliferation and migration during the development of the cerebral cortex.
Asunto(s)
Movimiento Celular/fisiología , Corteza Cerebral , Histona Demetilasas/metabolismo , Factor de Empalme Asociado a PTB/metabolismo , Células Piramidales/fisiología , Factores de Edad , Animales , Animales Recién Nacidos , Línea Celular , Movimiento Celular/genética , Corteza Cerebral/citología , Corteza Cerebral/embriología , Corteza Cerebral/crecimiento & desarrollo , Proteínas de Dominio Doblecortina , Electroporación , Embrión de Mamíferos , Regulación del Desarrollo de la Expresión Génica/genética , Regulación del Desarrollo de la Expresión Génica/fisiología , Histona Demetilasas/genética , Proteínas de Homeodominio/metabolismo , Antígeno Ki-67/metabolismo , Ratones , Proteínas Asociadas a Microtúbulos/metabolismo , Neuropéptidos/metabolismo , Proteínas Nucleares/metabolismo , Factor de Empalme Asociado a PTB/genética , ARN Interferente Pequeño/genética , ARN Interferente Pequeño/metabolismo , Proteínas Represoras/metabolismo , Factores de Transcripción SOXB1/metabolismoRESUMEN
Xp11.2 translocation-associated renal cell carcinoma (RCC) is a rare tumor that accounts for at least one-third of childhood RCC. Different reports have emphasized that previous radio/chemotherapy might be involved in its pathogenesis. We describe a child who developed a t(X;1)(p11.2;p34) associated RCC after previous treatment for genitourinary rhabdomyosarcoma in infancy. The presence of the PSF-TFE3 fusion has only been described in a very limited number of cases. Our report expands the spectrum of tumors in which RCC can arise in the pediatric age group after chemotherapy.