RESUMEN
The expansion of brain size is accompanied by a relative enlargement of the subventricular zone during development. Epithelial-like neural stem cells divide in the ventricular zone at the ventricles of the embryonic brain, self-renew and generate basal progenitors1 that delaminate and settle in the subventricular zone in enlarged brain regions2. The length of time that cells stay in the subventricular zone is essential for controlling further amplification and fate determination. Here we show that the interphase centrosome protein AKNA has a key role in this process. AKNA localizes at the subdistal appendages of the mother centriole in specific subtypes of neural stem cells, and in almost all basal progenitors. This protein is necessary and sufficient to organize centrosomal microtubules, and promote their nucleation and growth. These features of AKNA are important for mediating the delamination process in the formation of the subventricular zone. Moreover, AKNA regulates the exit from the subventricular zone, which reveals the pivotal role of centrosomal microtubule organization in enabling cells to both enter and remain in the subventricular zone. The epithelial-to-mesenchymal transition is also regulated by AKNA in other epithelial cells, demonstrating its general importance for the control of cell delamination.
Asunto(s)
Centrosoma/metabolismo , Proteínas de Unión al ADN/metabolismo , Ventrículos Laterales/citología , Ventrículos Laterales/embriología , Microtúbulos/metabolismo , Neurogénesis , Proteínas Nucleares/metabolismo , Factores de Transcripción/metabolismo , Animales , Movimiento Celular , Células Cultivadas , Células Epiteliales/metabolismo , Transición Epitelial-Mesenquimal , Humanos , Uniones Intercelulares/metabolismo , Interfase , Ventrículos Laterales/anatomía & histología , Glándulas Mamarias Animales/citología , Ratones , Tamaño de los Órganos , Organoides/citologíaRESUMEN
BACKGROUND AND PURPOSE: The aim of this work was to compare the accuracy of different HU adjustments for CBCT-based dose calculation. METHODS AND MATERIALS: Dose calculation was performed on CBCT images of 30 patients. In the first two approaches phantom-based (Pha-CC) and population-based (Pop-CC) conversion curves were used. The third method (WAB) represents override of the structures with standard densities for water, air and bone. In ROI mapping approach all structures were overridden with average HUs from planning CT. All techniques were benchmarked to the Pop-CC and CT-based plans by DVH comparison and γ-index analysis. RESULTS: For prostate plans, WAB and ROI mapping compared to Pop-CC showed differences in PTV D(median) below 2%. The WAB and Pha-CC methods underestimated the bladder dose in IMRT plans. In lung cases PTV coverage was underestimated by Pha-CC method by 2.3% and slightly overestimated by the WAB and ROI techniques. The use of the Pha-CC method for head-neck IMRT plans resulted in difference in PTV coverage up to 5%. Dose calculation with WAB and ROI techniques showed better agreement with pCT than conversion curve-based approaches. CONCLUSIONS: Density override techniques provide an accurate alternative to the conversion curve-based methods for dose calculation on CBCT images.