RESUMEN
Intricate cerebral cortex formation is orchestrated by the precise behavior and division dynamics of radial glial cells (RGCs). Endocytosis functions in the recycling and remodeling of adherens junctions (AJs) in response to changes in RGC activity and function. Here, we show that conditional disruption of ubiquitin-associated protein 1 (UBAP1), a component of endosomal sorting complex required for transport (ESCRT), causes severe brain dysplasia and prenatal ventriculomegaly. UBAP1 depletion disrupts the AJs and polarity of RGCs, leading to failure of apically directed interkinetic nuclear migration. Accordingly, UBAP1 knockout or knockdown results in reduced proliferation and precocious differentiation of neural progenitor cells. Mechanistically, UBAP1 regulates the expression and surface localization of cell adhesion molecules, and ß-catenin over-expression significantly rescues the phenotypes of Ubap1 knockdown in vivo. Our study reveals a critical physiological role of the ESCRT machinery in cortical neurogenesis by regulating AJs of RGCs.
Asunto(s)
Complejos de Clasificación Endosomal Requeridos para el Transporte , Células Ependimogliales , Femenino , Embarazo , Humanos , Células Ependimogliales/metabolismo , Complejos de Clasificación Endosomal Requeridos para el Transporte/metabolismo , Ubiquitina/metabolismo , Uniones Adherentes/metabolismo , Corteza Cerebral/metabolismo , Neurogénesis , Proteínas Portadoras/metabolismoRESUMEN
OBJECTIVE: Prenatal ventriculomegaly (VM) is classified as mild, moderate, or severe on the basis of the diameter of the atrium. Neurodevelopmental status in prenatal VM is associated with various factors such as the course of VM, VM type, progression, and associated anomalies. In this study, the authors aimed to evaluate neurodevelopmental outcome in patients with prenatal VM and to detect possible associated risk factors. METHODS: In this study, 73 pregnancies with VM who were referred to Children's Medical Center, Tehran, Iran, between 2019 and 2021 were prospectively followed. They were followed up every 2-4 weeks with ultrasonography (US) before delivery and were then observed for an average time of 14.6 months. The authors collected demographic and ultrasound information, associated abnormalities, pregnancy outcomes, and developmental status according to Centers for Disease Control criteria. RESULTS: The mean gestational age at the time of diagnosis was 28.1 weeks, and 46.6% of fetuses were female. According to the first US, 46.6% had mild, 21.9% had moderate, and 31.5% had severe VM. Serial US scans showed that VM had regressed in 20.5% of patients, remained stable in 35.6%, and progressed in 43.8%. Other cranial abnormalities were detected in 38.4% of fetuses. During follow-up, 62.5% of cases had normal developmental status, 26.6% had mild delay, and 10.9% had severe neurodevelopmental delay. Pregnancy was terminated in 9 (12.3%) cases. Normal neurodevelopment was reported in 75.8% of patients with mild VM versus 50% of those with severe VM (p = 0.19). Neurodevelopmental status was normal in 72.5% of cases without other cranial abnormalities (p = 0.018) and in 86.7% of cases with regression of VM (p = 0.028). CONCLUSIONS: Despite analysis of different factors in prenatal VM, only progression of VM and associated cranial abnormalities had significant relationships with neurodevelopmental prognosis.
Asunto(s)
Hidrocefalia , Malformaciones del Sistema Nervioso , Embarazo , Niño , Humanos , Femenino , Masculino , Estudios Prospectivos , Ultrasonografía Prenatal , Irán , Hidrocefalia/complicaciones , Resultado del Embarazo , Diagnóstico PrenatalRESUMEN
OBJECTIVE: Prenatal ventriculomegaly is classified as mild, moderate, or severe based on the atrium diameter. The natural course and intrauterine progression of mild and moderate ventriculomegaly associated with the neurodevelopmental status of these children has been widely reported. METHODS: One hundred twenty-two pregnancies with mild and moderate ventriculomegaly referred to the pediatric neurosurgery clinic of Children's Medical Center between 2010 and 2018 were retrospectively studied. The authors collected demographic and first and sequential ultrasonographic information, associated abnormalities, information about pregnancy outcomes, and the latest developmental status of these children according to Centers for Disease Control and Prevention criteria by calling parents at least 1 year after birth. RESULTS: The mean gestational age at the time of diagnosis was 29.1 weeks, and 53% of fetuses were female. The width of the atrium was registered precisely in 106 cases, in which 61% had mild and 39% had moderate ventriculomegaly. Information on serial ultrasound scans was collected in 84 cases in which ventriculomegaly regressed in 5, remained stable in 67, and progressed in 12 patients. Fourteen cases (29.7%) in the mild ventriculomegaly group and 6 cases (16.2%) in the moderate group had associated abnormalities, with corpus callosum agenesis as the most frequent abnormality. The survival rate was 80% in mild and 89.4% in moderate ventriculomegaly. Considering survival to live birth and progression of the ventriculomegaly, the survival rate was 100% in regressed, 97% in stable, and 41.6% in progressed ventricular width groups (p < 0.001). Neurodevelopmental status was evaluated in 73 cases and found to be normal in 69.8% of the cases; 16.4% of children had mild delay, and 5.4% and 8.2% of cases were diagnosed with moderate and severe delays, respectively. CONCLUSIONS: In spite of a high rate of missed data in our retrospective study, most patients with mild or moderate ventriculomegaly had a stable or regressed course. Most cases had near-normal developmental status. Prospective studies with a larger sample size and detailed developmental evaluation tests are needed to answer the questions related to the natural course, survival, and prognosis of prenatal ventriculomegaly.