Nuclear Segmentation, Condensation and Bilateral Symmetry in Polymorphonuclear Leukocytes Reflect Genomic Order and Favor Immunologic Function

Abstract

Segmentation, condensation and bilateral symmetry of the nuclei of polymorphonuclear leukocytes seem related to their function. Segmentation of the nuclei into two or more lobes and their condensation facilitate their passage (diapedesis) through the endothelial layer of blood vessels to the extravasal space and subsequent locomotion through the interstitial compartment of different tissues. Bilateral symmetry of these nuclei along with their association to the cytoskeletal fibers contribute to their efficiency in locomotion by alignment of the axis of nuclear symmetry to the axis of cellular polarity, which orients towards the direction of locomotion in response to cytokines and other stimuli. Observations of the cytogenetic facets of intranuclear order support these assumptions.

Chromosomes in a genome-wise order: evidence for metaphase architecture

“…In earlier studies by methylation staining of mammalian spermatocytes as well as early embryonic cells the parental order and genomic separation of parental chromosome sets were detected [ 24 ]. While this parentally derived methylation pattern disappeared after the four-cell stage, the chromosomes still remained aligned during interphase (chromosome territories) and even during metaphase as suggested by us previously [ 7 , 10 – 13 ].…”

“…Although not stated, this model already suggests the organization of chromosomes in two haploid sets as indicated by us [ 7 ]. The last model also predicts the presence of a certain architecture of CTs in both interphase and metaphase in the way of a haploid grouping, which beyond human samples [ 7 – 13 ] was also found in plant louse cells [ 17 ], rat liver cells [ 14 , 15 ] and in hexaploid vole cells [ 16 ]. …”

“…From a variety of human samples, which include numerically and structurally abnormal human karyotypes and also in those derived from other species, including primates and mice the following implications can be assigned as a general model for metaphase architecture: Metaphase spreads show a more or less round shape similar to interphase nuclei, which in 3D represents a symmetrical distribution of the chromosomal DNA (Additional file 7 : Figure S6). Interestingly, a round shape and equal DNA distribution can also be observed in so called “rosette” orientation of metaphase spreads, known classically as metaphase plates, where chromosome haplosets are arranged in a mirror wise order of homologous chromosomes [ 7 , 11 , 13 ]. This has already been observed in vivo and documented by the founder of cytogenetics Walther Flemming in salamander larva (Additional file 8 : Figure S7) and quite recently by our group [ 13 ].…”

“…Interestingly, a round shape and equal DNA distribution can also be observed in so called “rosette” orientation of metaphase spreads, known classically as metaphase plates, where chromosome haplosets are arranged in a mirror wise order of homologous chromosomes [ 7 , 11 , 13 ]. This has already been observed in vivo and documented by the founder of cytogenetics Walther Flemming in salamander larva (Additional file 8 : Figure S7) and quite recently by our group [ 13 ]. The bilateral symmetry line often reflects a mirror line dividing two homologous chromosomes located next to each other (Figs.…”

“…A non-random distribution of chromosomes was suggested already in the early days of human cytogenetics [ 5 , 6 ]; however, majority of cytogeneticists commonly accept that chromosomes in a metaphase spread are generally arranged completely haphazardly. Based on the observation of the bilaterally symmetric distribution of DNA and chromosome specific FISH signals in leukocytes, we demonstrated in a series of publications [ 7 – 13 ] a genome-wise organization of chromosomes in human and murine cells. In other words, the parental haploid chromosome sets of diploid cells are well arranged within the nucleus and also within the metaphase stage, when DNA is most condensed and appears as microscopically visible chromosomes.…”