Biology subjects

Harris, W. A.

Publications and source records attributed to Harris, W. A..

3 recordsLinked to original sources

bioRxiv2019

Interkinetic nuclear migration in the zebrafish retina as a diffusive process

A major hallmark of neural development is the oscillatory movement of nuclei between the apical and basal surfaces of the neuroepithelium during the process of interkinetic nuclear migration (IKNM). Here, we employ long-term, rapid lightsheet and two-photon imaging of Zebrafish retinas in vivo during early development to uncover the physical processes that govern the behavior of nuclei during IKNM. These images allow the capture of reliable tracks of nuclear movements and division during early retinogenesis for many tightly packed nuclei. These tracks are then used to create and test a theory of retinal IKNM as a diffusive process across a nuclear concentration gradient generated by the addition of new nuclei at the apical surface. The analysis reveals the role of nuclear packing at the apical surface on the migration dynamics of nuclei, provides a robust quantitative explanation for the distribution of nuclei across the retina, and may have implications for stochastic fate choice in this system.

developmental biology↗

bioRxiv2018

On-site ribosome remodeling by locally synthesized ribosomal proteins in axons

Ribosomes are known to be assembled in the nucleolus, yet recent studies have revealed robust enrichment and translation of mRNAs encoding ribosomal proteins (RPs) in axons, far away from neuronal cell bodies. Using subcellular proteomics and live-imaging, we show that locally synthesized RPs incorporate into axonal ribosomes in a nucleolus-independent fashion. We revealed that axonal RP translation is regulated through a novel sequence motif, CUIC, that forms a RNA-loop structure in the region immediately upstream of the initiation codon. Inhibition of axonal CUIC-regulated RP translation leads to defects in local translation activity and axon branching, demonstrating the physiological relevance of the axonal ribosome remodeling. These results indicate that axonal translation supplies cytoplasmic RPs to maintain/modify local ribosomal function far from the nucleolus.

neuroscience↗

bioRxiv2018

Genetic control of cellular morphogenesis in Müller glia

Of all the cells in the body, those with the greatest variety of shapes reside in the central nervous system yet they all start their postmitotic lives as simple elongated cells of the neuroepithelium1.The molecular processes by which these, or indeed any, cells gain their particular cell-specific anatomies remain largely unexplored.We, therefore, developed a strategy to identify the genes involved in cellular morphogenesis using Muller glial (MG) cells in the vertebrate retina as a model system.These radially oriented cells, discovered by Heinrich Muller in 1851 and named in his honour2, are astonishingly complex yet, as the great neurohistologist Ramon y Cajal first noted, they share a conserved set of key anatomical features3.Using genomic and CRISPR based strategies in zebrafish, combined with a temporal dissection of the process, we found more than 40 genes involved in MG cell morphogenesis.Strikingly, the sequential steps of anatomical feature addition are regulated by successive expression of cohorts of interrelated genes, revealing unprecedented insights into the developmental genetics of cellular morphogenesis.

cell biology↗