MR and CT Evaluation of Dysembryoplastic Neuroepithelial Tumor

A 33-year-old man presented with a long history of intractable partial seizures with the first episode at the age of 18 years. The seizure frequency had increased in the recent past. CT imaging revealed a low attenuation lesion in the left frontal cortex with calvarial scalloping. MR imaging revealed a heterogeneous signal intensity lesion with involvement of the cortex and the sub-cortical white matter. In dysembryoplastic neuroepithelial tumor the neoplastic elements adjacent to the cortex might cause disorganization of cortical layers in the developmental stage leading to cortical dysplasia. Architectural dysplasia is characterized by cortical thickening and ectopic neurons in the white matter. MR imaging features reflect the characteristics of cortical dysplasia and ectopic neurons in the sub-cortical white matter.

Tufted Is a Gain-of-Function Allele That Promotes Ectopic Expression of the Proneural Gene amos in Drosophila

The Tufted1 (Tft1) dominant mutation promotes the generation of ectopic bristles (macrochaetae) in the dorsal mesothorax of Drosophila. Here we show that Tft1 corresponds to a gain-of-function allele of the proneural gene amos that is associated with a chromosomal aberration at 36F-37A. This causes ectopic expression of amos in large domains of the lateral-dorsal embryonic ectoderm, which results in supernumerary neurons of the PNS, and in the notum region of the third instar imaginal wing, which gives rise to the mesothoracic extra bristles. Revertants of Tft1, which lack ectopic neurons and bristles, do not show ectopic expression of amos. One revertant is a loss-of-function allele of amos and has a recessive phenotype in the embryonic PNS. Our results suggest that both normal and ectopic Tft1 bristles are generated following similar rules, and both are subjected to Notch-mediated lateral inhibition. The ability of Tft1 bristles to appear close together may be due to amos having a stronger proneural capacity than that of other proneural genes like asense and scute. This ability might be related to the wild-type function of amos in promoting development of large clusters of closely spaced olfactory sensilla.

parachute/n-cadherinis required for morphogenesis and maintained integrity of the zebrafish neural tube

N-cadherin (Ncad) is a classical cadherin that is implicated in several aspects of vertebrate embryonic development, including somitogenesis, heart morphogenesis, neural tube formation and establishment of left-right asymmetry. However, genetic in vivo analyses of its role during neural development have been rather limited. We report the isolation and characterization of the zebrafish parachute (pac) mutations. By mapping and candidate gene analysis, we demonstrate that pac corresponds to a zebrafish n-cadherin (ncad) homolog. Three mutant alleles were sequenced and each is likely to encode a non-functional Ncad protein. All result in a similar neural tube phenotype that is most prominent in the midbrain, hindbrain and the posterior spinal cord. Neuroectodermal cell adhesion is altered, and convergent cell movements during neurulation are severely compromised. In addition, many neurons become progressively displaced along the dorsoventral and the anteroposterior axes. At the cellular level, loss of Ncad affects β-catenin stabilization/localization and causes mispositioned and increased mitoses in the dorsal midbrain and hindbrain, a phenotype later correlated with enhanced apoptosis and the appearance of ectopic neurons in these areas. Our results thus highlight novel and crucial in vivo roles for Ncad in the control of cell convergence, maintenance of neuronal positioning and dorsal cell proliferation during vertebrate neural tube development.

Distinct effects of XBF-1 in regulating the cell cycle inhibitor p27(XIC1) and imparting a neural fate

XBF-1 is an anterior neural plate-specific, winged helix transcription factor that affects neural development in a concentration-dependent manner. A high concentration of XBF-1 results in suppression of endogenous neuronal differentiation and an expansion of undifferentiated neuroectoderm. Here we investigate the mechanism by which this expansion is achieved. Our findings suggest that XBF-1 converts ectoderm to a neural fate and it does so independently of any effects on the mesoderm. In addition, we show that a high dose of XBF-1 promotes the proliferation of neuroectodermal cells while a low dose inhibits ectodermal proliferation. Thus, the neural expansion observed after high dose XBF-1 misexpression is due both to an increase in the number of ectodermal cells devoted to a neural fate and an increase in their proliferation. We show that the effect on cell proliferation is likely to be mediated by p27(XIC1), a cyclin-dependent kinase (cdk) inhibitor. We show that p27(XIC1) is expressed in a spatially restricted pattern in the embryo, including the anterior neural plate, and when misexpressed it is sufficient to block the cell cycle in vivo. We find that p27(XIC1)is transcriptionally regulated by XBF-1 in a dose-dependent manner such that it is suppressed or ectopically induced by a high or low dose of XBF-1, respectively. However, while a low dose of XBF-1 induces ectopic p27(XIC1)and ectopic neurons, misexpression of p27(XIC1)does not induce ectopic neurons, suggesting that the effects of XBF-1 on cell fate and cell proliferation are distinct. Finally, we show that p27(XIC1)is suppressed by XBF-1 in the absence of protein synthesis, suggesting that at least one component of p27(XIC1)regulation by XBF-1 may be direct. Thus, XBF-1 is a neural-specific transcription factor that can independently affect both the cell fate choice and the proliferative status of the cells in which it is expressed.