Inhibition of Foxp4 Disrupts Cadherin-based Adhesion of Radial Glial Cells, Leading to Abnormal Differentiation and Migration of Cortical Neurons in Mice / 神经科学通报·英文版

Heterozygous loss-of-function variants of FOXP4 are associated with neurodevelopmental disorders (NDDs) that exhibit delayed speech development, intellectual disability, and congenital abnormalities. The etiology of NDDs is unclear. Here we found that FOXP4 and N-cadherin are expressed in the nuclei and apical end-feet of radial glial cells (RGCs), respectively, in the mouse neocortex during early gestation. Knockdown or dominant-negative inhibition of Foxp4 abolishes the apical condensation of N-cadherin in RGCs and the integrity of neuroepithelium in the ventricular zone (VZ). Inhibition of Foxp4 leads to impeded radial migration of cortical neurons and ectopic neurogenesis from the proliferating VZ. The ectopic differentiation and deficient migration disappear when N-cadherin is over-expressed in RGCs. The data indicate that Foxp4 is essential for N-cadherin-based adherens junctions, the loss of which leads to periventricular heterotopias. We hypothesize that FOXP4 variant-associated NDDs may be caused by disruption of the adherens junctions and malformation of the cerebral cortex.

Expression and clinical significance of p57KIP2,cyclin D1,and cyclin E in male breast can-cer / 中国肿瘤临床

Objective:To explore the relationship between the expression of p57KIP2,cyclin D1,and cyclin E receptors in male breast can-cer(MBC)and its clinical significance.Methods:Data of MBC cases diagnosed in The First Affiliated Hospital of Wenzhou Medical Uni-versity between January 2000 and December 2016 were reviewed.Forty cases of infiltrating ductal carcinoma(IDC)and 20 cases of male ductal carcinoma in situ(DCIS)were selected,and 20 cases of gynecomastia(GYM)were selected as controls.The expression of p57KIP2,cyclin D1,and cyclin E mRNA and protein in the tissue samples obtained from IDC,DCIS,and GYM cases were measured by re-verse transcription polymerase chain reaction and immunohistochemistry,respectively.Results:The expression of p57KIP2mRNA in IDC was 0.18±0.07,which was lower than that in DCIS(0.42±0.05)and GYM(0.75±0.04).The rate of p57KIP2positivity in IDC was 25%(10/40),which was lower than that in DCIS 60%(12/20)and GYM 90%(18/20).There were significant differences in the expression of p57KIP2mRNA and protein among the three groups(P<0.05).The expression of cyclin D1 and cyclin E mRNA in IDC was 0.92±0.12 and 0.96±0.08,which was higher than that in DCIS(0.72±0.06,0.64±0.01)and GYM(0.38±0.03,0.21±0.02),respectively.Cyclin D1 and cy-clin E protein positive rates in IDC were 90%(36/40)and 88%(35/40),which were higher than those in DCIS[80%(16/20),85%(17/20)],and GYM[25%(5/20),20%(4/20)].In IDC tissues,the expression of p57KIP2,cyclin D1,and cyclin E proteins was associated with the clinical stage and histological grade(P<0.05),and the expression of p57KIP2protein was correlated with axillary node metastasis(P<0.05).There was a negative correlation between the expression of p57KIP2and cyclin D1 and between p57KIP2and cyclin E.However,the correlation between cyclin D1 and cyclin E expression was positive(P<0.05).Conclusions:p57KIP2,cyclin D1,and cyclin E may play an im-portant role in the development and progression of MBC.Combined clinicopathological detection of p57KIP2,cyclin D1,and cyclin E can aid future research on MBC.