Biology subjects

Cerveny, K.

Publications and source records attributed to Cerveny, K..

3 recordsLinked to original sources

bioRxiv2026

Optic nerve innervation promotes Wnt/b-catenin pathway activity and progenitor cell proliferation in the zebrafish optic tectum

In the zebrafish visual system, accurate retinotopic mapping occurs throughout life as new neurons are generated and integrated into existing circuitry in both the retina and optic tectum (OT). To explore how OT development changes relative to innervation from the retina, we examined cell death and proliferation in genetic and surgical models that disrupt retinal innervation of the OT. Specifically, we compared lakritz (lak) mutants, which have no optic nerves due to a lesion in the atoh7 gene, with either wild-type or one-eyed fish generated through surgical eye removal. We observed elevated cell death, fewer proliferating progenitors, and fewer sox2+ OT neuroepithelial stem cells in lak mutant and denervated OT lobes. To examine whether light-mediated vision contributes to proliferation and survival in the optic tectum, we reared fish in constant darkness and then compared survival and proliferation of OT cells in innervated and non-innervated tecta. We found that OT cells were still more likely to survive and proliferate in the presence of optic nerve innervation even when fish were reared in the dark. To identify molecular pathways that could regulate OT growth, we examined the expression of known mitogens in the zebrafish optic tectum and found evidence that Wnt/{beta}-catenin pathway activity could promote innervation-dependent proliferation in lak mutant tecta. Expression of both wnt3a and the Wnt/{beta}-catenin target gene axin2, as detected by in situ hybridization and RT-qPCR, is decreased in non-innervated tectal lobes. Further supporting an innervation-dependent role for Wnt/{beta}-catenin pathway activation in the zebrafish OT, we found that lak mutants treated with a Wnt-pathway agonist, BIO, exhibited levels of OT cell proliferation that were indistinguishable from wild-type. Together these findings suggest that progenitor cells in the optic tectum produce Wnt3a in response to innervation by the optic nerve, providing new insight into how a vertebrate visual system coordinates growth across its sensory and recipient tissues.

Developmental Biology↗

bioRxiv2019

Loss of cell cycle control renders cells nonresponsive to local extrinsic differentiation cues

Objective and approachesAberrantly proliferating cells are linked to a number of diseases including cancers and developmental defects.To determine the extent to which local extrinsic signals contribute to or ameliorate mutant cell behaviors, we examined survival and differentiation of mutant cells in wild-type retinal environments by generating chimeric zebrafish embryos comprised of unlabeled host cells and GFP-labeled neural progenitor donor cells. In addition, we examined the fate of retinal progenitor cells when cdkn1c, a cyclin dependent kinase inhibitor, was induced in clones within wild-type and hdac1 mutant retinae.\n\nResultsWe found that seven of the ten mutants examined exhibited apoptosis when grafted into wild-type tissue, with cells from two slowly cycling mutants, elys and emi1, noticeably differentiating in a wild-type environment. Observations of the one hyperproliferative mutant, hdac1, revealed that these mutant cells did not appear to die or differentiate but instead survived and formed tumor-like rosettes in a wild-type environment. Ectopic expression of cdkn1c was unable to force cell cycle exit and differentiation of the majority of hdac1 mutant cells.\n\nConclusionsTogether, these results suggest that although a wild-type environment rarely encourages cell cycle exit and differentiation of neural progenitors with cell cycle defects, wild-type survival signals may enable hyperproliferative progenitor cells to persist instead of die.

developmental biology↗

bioRxiv2018

Abrogation of Stem Loop Binding Protein (Slbp) function leads to a failure of cells to transition from proliferation to differentiation, retinal coloboma and midline axon guidance deficits.

Through forward genetic screening for mutations affecting visual system development, we identified prominent coloboma and cell-autonomous retinal neuron differentiation, lamination and retinal axon projection defects in eisspalte (ele) mutant zebrafish. Additional axonal deficits were present, most notably at midline axon commissures. Genetic mapping and cloning of the ele mutation showed that the affected gene is slbp, which encodes a conserved RNA stem-loop binding protein involved in replication dependent histone mRNA metabolism. Cells throughout the central nervous system remained in the cell cycle in ele mutant embryos at stages when, and locations where, post-mitotic cells have differentiated in wild-type siblings. Indeed, RNAseq analysis showed down-regulation of many genes associated with neuronal differentiation. This was coincident with changes in the levels and spatial localisation of expression of various genes implicated, for instance, in axon guidance, that likely underlie specific ele phenotypes. These results suggest that many of the cell and tissue specific phenotypes in ele mutant embryos are secondary to altered expression of modules of developmental regulatory genes that characterise, or promote transitions in, cell state and require the correct function of Slbp-dependent histone and chromatin regulatory genes.\n\nAuthor SummaryCongenital deficits of eye formation are common in humans and to help understand the genetic basic of such conditions, we are studying zebrafish with comparable eye defects. We identified defects in both the shaping of the eye and in its connections to the brain in eisspalte mutant fish. Further analyses revealed additional deficits in the brain, most notably a severe reduction in neurons and their connections. We find that this is due to an inability of the cells that generate neurons to transition from proliferation to neuronal differentiation. By using a sequencing approach to compare mutant embryos to their normal siblings, we identified the affected gene as slbp, which encodes a protein that binds the mRNAs of other genes important for cell proliferation. This sequencing approach revealed the full extent of changes in gene expression in the mutant, helping us to better understand why the nervous system defects occur. Our study suggests that in the absence of Slbp function, cells lose the ability to transition from the proliferative to the differentiated state and this leads to additional defects in the eyes and brain.

genetics↗