Morphogenesis of the lateral geniculate nucleus in primates

The lateral geniculate nucleus (LGN) is the part of the mammalian visual system that relays information from the eye to the cerebral cortex. In the rhesus macaque monkey, the LGN exhibits an intricate lamination pattern, which changes midway through the nucleus at a point coincident with small gaps due to the blind spot in the retina. This thesis investigates the hypothesis that the singularities produced by the gaps induce the laminar transition at its normal location. A three-dimensional model of the LGN morphogenesis is developed, in which local cell interactions cause a wave of development of neuronal receptive fields to propagate through the nucleus and establish two distinct lamination patterns. Analysis of the underlying dynamics helps understand the mechanism of propagation of the developmental wave, as well as the mechanism which allows a localized anomaly to trigger a lamination transition and cause the boundary between the lamination patterns to propagate across the nucleus. This is probably the first time the three-dimensional morphogenesis of a brain structure has been modeled in a detailed, biologically-realistic framework.The LGN morphology in two other primates, chimpanzee and human, was also analyzed in real tissue sections, as well as in sections of a three-dimensional, computer reconstruction of human LGN. Despite different locations of the blind spot in the retina of the three primates, the same co-localization of the gaps and the transition surface is found in all three species. This result eliminates the possibility of feature co-localization due to chance. The primate LGN morphology provides a rare, but compelling biological example of a physical principle, namely, that the boundary conditions or singularities may have an extended effect over the state of the entire system.U of I OnlyETDs are only available to UIUC Users without author permissio

Circulating Histones to Detect and Monitor the Progression of Cancer

Liquid biopsies have emerged as a minimally invasive cancer detection and monitoring method, which could identify cancer-related alterations in nucleosome or histone levels and modifications in blood, saliva, and urine. Histones, the core component of the nucleosome, are essential for chromatin compaction and gene expression modulation. Increasing evidence suggests that circulating histones and histone complexes, originating from cell death or immune cell activation, could act as promising biomarkers for cancer detection and management. In this review, we provide an overview of circulating histones as a powerful liquid biopsy approach and methods for their detection. We highlight current knowledge on circulating histones in hematologic malignancies and solid cancer, with a focus on their role in cancer dissemination, monitoring, and tumorigenesis. Last, we describe recently developed strategies to identify cancer tissue-of-origin in blood plasma based on nucleosome positioning, inferred from nucleosomal DNA fragmentation footprint, which is independent of the genetic landscape