title: Heterogenic final cell cycle by chicken retinal Lim1 horizontal progenitor cells leads to heteroploid cells with a remaining replicated genome.
abstract: Retinal progenitor cells undergo apical mitoses during the process of interkinetic nuclear migration and newly generated post-mitotic neurons migrate to their prospective retinal layer. Whereas this is valid for most types of retinal neurons, chicken horizontal cells are generated by delayed non-apical mitoses from dedicated progenitors. The regulation of such final cell cycle is not well understood and we have studied how Lim1 expressing horizontal progenitor cells (HPCs) exit the cell cycle. We have used markers for S- and G2/M-phase in combination with markers for cell cycle regulators Rb1, cyclin B1, cdc25C and p27Kip1 to characterise the final cell cycle of HPCs. The results show that Lim1+ HPCs are heterogenic with regards to when and during what phase they leave the final cell cycle. Not all horizontal cells were generated by a non-apical (basal) mitosis; instead, the HPCs exhibited three different behaviours during the final cell cycle. Thirty-five percent of the Lim1+ horizontal cells was estimated to be generated by non-apical mitoses. The other horizontal cells were either generated by an interkinetic nuclear migration with an apical mitosis or by a cell cycle with an S-phase that was not followed by any mitosis. Such cells remain with replicated DNA and may be regarded as somatic heteroploids. The observed heterogeneity of the final cell cycle was also seen in the expression of Rb1, cyclin B1, cdc25C and p27Kip1. Phosphorylated Rb1-Ser608 was restricted to the Lim1+ cells that entered S-phase while cyclin B1 and cdc25C were exclusively expressed in HPCs having a basal mitosis. Only HPCs that leave the cell cycle after an apical mitosis expressed p27Kip1. We speculate that the cell cycle heterogeneity with formation of heteroploid cells may present a cellular context that contributes to the suggested propensity of these cells to generate cancer when the retinoblastoma gene is mutated.
authors.affiliation: Department of Neuroscience, Uppsala University, Uppsala, Sweden.
authors.forename: Shahrzad
authors.initials: S
authors.lastname: Shirazi Fard
authors.forename: Miguel
authors.initials: M
authors.lastname: Jarrin
authors.forename: Henrik
authors.initials: H
authors.lastname: Boije
authors.forename: Valerie
authors.initials: V
authors.lastname: Fillon
authors.forename: Charlotta
authors.initials: C
authors.lastname: All-Eriksson
authors.forename: Finn
authors.initials: F
authors.lastname: Hallböök
mesh_terms: D000818:Animals; D016203:CDC2 Protein Kinase / Q000235:genetics / Q000378:metabolism; D002453:Cell Cycle / Q000502:physiology*; D002467:Cell Nucleus / Q000378:metabolism; D002642:Chick Embryo; D002875:Chromosomes; D056744:Cyclin B1 / Q000235:genetics / Q000378:metabolism; D050760:Cyclin-Dependent Kinase Inhibitor p27 / Q000235:genetics / Q000378:metabolism; D004261:DNA Replication; D005260:Female; D015870:Gene Expression; D016678:Genome; D018398:Homeodomain Proteins / Q000378:metabolism; D060850:LIM-Homeodomain Proteins / Q000378:metabolism*; D008297:Male; D008938:Mitosis / Q000502:physiology; D011003:Ploidies; D012160:Retina / Q000166:cytology / Q000378:metabolism; D051248:Retinal Horizontal Cells / Q000378:metabolism*; D016160:Retinoblastoma Protein / Q000235:genetics / Q000378:metabolism; D016196:S Phase; D013234:Stem Cells / Q000378:metabolism*; D025521:Tumor Suppressor Proteins / Q000378:metabolism; D020687:cdc25 Phosphatases / Q000378:metabolism; D000098551:Prospero-Related Homeobox 1 Protein
chemical_list: D056744:Cyclin B1; D018398:Homeodomain Proteins; D060850:LIM-Homeodomain Proteins; D016160:Retinoblastoma Protein; D025521:Tumor Suppressor Proteins; D000098551:Prospero-Related Homeobox 1 Protein; D050760:Cyclin-Dependent Kinase Inhibitor p27; D016203:CDC2 Protein Kinase; D020687:cdc25 Phosphatases