An investigation of the changes taking place in the enamel and the enamel organ during enamel development has been carried out by analyzing small samples of tissue dissected from developing incisors of rat and bovine incisors. Observations showed that the synthesis of the enamel matrix and its subsequent loss were associated chiefly with a change in the major matrix components. This consisted of a selective loss of amelogenin components prior to secondary mineralization. Before this loss, some increase in the proportion of smaller molecular weight components suggested the possibility of limited breakdown. Even at the earliest stages examined, significant concentration of mineral ions was present. This increased steeply after most of the organic matrix had been removed. The Ca/P ratio of this mineral was constant throughout development. The concentration of minor inorganic ions (F, Mg and CO3) decreased as the tissue developed and a tendency was observed for certain ions (F, 32PO4) to penetrate and concentrate in the enamel, apparently as a consequence of the lost matrix being replaced by water, just prior to the steep increase in mineral content of the tissue.
By avoiding chemical fixation and using a freeze-drying technique, it proved possible to examine the enamel organ of rat mandibular incisors histologically while retaining the adjacent enamel of the same tooth for chemical analysis. The dramatic alterations which occur in enamel organ histology, such as ameloblast shortening and the development of hte papillary layer, could then be compared directly with mineral uptake and mineral content of the adjacent enamel. Both enamel and adjacent enamel organ were sampled as a continuous series of pieces, 0.5 mm in width, from youngest (apical) to oldest (incisal) tissue. Short ameloblasts were associated directly with the beginning of a rapid uptake of phosphate ions during the maturation phase and also coincided with the beginning of a steep rise in mineral content. By implication, some loss of matrix may also occur at this point. Development of the highly vascular papillary layer preceded ameloblast shortening and may be associated with changes in the organic matrix prior to its disappearance from the tissue. Further development of this layer was associated with ameloblast shortening. This may also therefore be associated with mineral uptake during maturation.
Overexpression and mitosis-promoting roles of Transforming acidic coiled-coil containing protein 3 (TACC3) are well-established in many cancers, including glioblastoma (GBM). However, the effector gene networks downstream of TACC3 remain poorly defined, partly due to an incomplete understanding of TACC3 cell lineage specificity and its dynamic role during the cell cycle. Here, we use a patient-derived GBM model to report that TACC3 predominantly resides in the GBM cell cytoplasm, while engaging in gene regulation temporally as defined by the cell cycle state. TACC3 loss-of-function, cell cycle stage-specific transcriptomics, and unsupervised self-organizing feature maps revealed pathways (including Hedgehog signalling) and individual genes (including HOTAIR) that exhibited anticorrelated expression phenotypes across interphase and mitosis. Furthermore, this approach identified a set of 22 TACC3-dependent transcripts in publicly-available clinical databases that predicted poor overall and progression-free survival in 162 GBM and 514 low-grade glioma patient samples. These findings uncover TACC3-dependent genes as a function of TACC3 cell cycle oscillation, which is important for TACC3-targeting strategies, and for predicting poor outcomes in brain cancer patients.
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