Biology subjects

Zhong, J.

Publications and source records attributed to Zhong, J..

5 recordsLinked to original sources

bioRxiv2018

Deficient FGF signaling in the developing peripheral retina disrupts ciliary margin development and causes aniridia

The mammalian ciliary margin is a part of the developing peripheral neural retina that differentiates into the ciliary body and the iris. Canonical WNT signaling plays a critical role in the specification of the ciliary margin at the peripheral retina in the presence of strong FGF signaling in the central retina. The mechanism of how the boundary between the central retina and the ciliary margin is created has not been previously elucidated. Using genetic ablation and epistasis experiments, we show that loss of FGF signaling gradient in the peripheral retina causes expansion of WNT signaling towards the central retina thereby disrupting the neurogenic boundary and compartmentalization of the ciliary margin. Loss of WNT signaling displays a complimentary effect with expansion of FGF signaling into the ciliary marginal space. Using in vivo experiments, we elucidate the FGF signaling cascade involved in development of the ciliary margin. We also identify the surface ectoderm as the source of WNT ligands in eliciting WNT response at the ciliary margin. We show that an interaction between FGF and WNT signaling is required for generation of the ciliary marginal cells. Taken together, our results reveal that a gradient intersection of FGF and WNT signaling is required for specification of the ciliary margin.

developmental biology↗

bioRxiv2018

Strain maps characterize the symmetry of convergence and extension patterns during Zebrafish gastrulation

During gastrulation of the zebrafish embryo, the cap of blastoderm cells organizes into the axial body plan of the embryo with left-right symmetry and head-tail, dorsal-ventral polarities. Our labs have been interested in the mechanics of early development and have investigated whether these large-scale cells movements can be described as tissue-level mechanical strain by a tectonics-based approach. The first step is to image the positions of all nuclei from mid-epiboy to early segmentation by digital sheet light microscopy (DSLM), organize the surface of the embryo into multi-cell spherical domains, construct velocity fields from the movements of these domains and extract 3D strain rate maps. Tensile/expansive and compressive strains in the axial and equatorial directions are detected during gastrulation as anterior and posterior expansion along the anterior-posterior axis and medial-lateral compression across the dorsal-ventral axis corresponding to convergence and extension. In later stages in development are represented by localized medial expansion at the onset of segmentation and anterior expansion at the onset of neurulation. Symmetric patterns of rotation are first detected in the animal hemispheres at mid-epiboly and then the vegetal hemispheres by the end of gastrulation. By analysing the temporal sequence of large scale movements, deformations across the embryo can be attributed to a combination of epiboly and dorsal convergence-extension.\n\nSignificanceStrain is an emergent property of tissues that originates from the mechanical coupling of cell-cell and cell-substrate interactions, individual cell shape changes, and cell level forces. By imaging the positions of nuclei from mid-epiboly to early segmentation of the zebrafish embryo we are able to calculate three types of strain maps by a plate tectonics based method. The regions of expansive and compressive axial and equatorial strain correspond to areas undergoing convergence and extension, a major step in the formation of the embryonic body plan as well as the formation of somite and head structures. The most striking signatures of strain are: 1. the bilateral symmetry of linear strain across the anterior-posterior, dorsal-ventral axis during gastrulation, 2. the complementary counter-rotational strains or curl in the animal hemisphere at mid epiboly, and 3. a divergence or saddle point in the region of the dorsal organizer, head-trunk boundary. These strains represent a general method to describe large-scale tissue-level mechanics not only of embryonic development but also tissue homeostasis and disease.

biophysics↗

bioRxiv2018

Single-cell RNA-seq reveals dynamic transcriptome profiling in human early neural differentiation

BackgroundInvestigating cell fate decision and subpopulation specification in the context of the neural lineage is fundamental to understanding neurogenesis and neurodegenerative diseases. The differentiation process of neural-tube-like rosettes in vitro is representative of neural tube structures, which are composed of radially organized, columnar epithelial cells and give rise to functional neural cells. However, the underlying regulatory network of cell fate commitment during early neural differentiation remains elusive.\n\nResultsIn this study, we investigated the genome-wide transcriptome profile of single cells from six consecutive reprogramming and neural differentiation time points and identified cellular subpopulations present at each differentiation stage. Based on the inferred reconstructed trajectory and the characteristics of subpopulations contributing the most towards commitment to the central nervous system (CNS) lineage at each stage during differentiation, we identified putative novel transcription factors in regulating neural differentiation. In addition, we dissected the dynamics of chromatin accessibility at the neural differentiation stages and revealed active c/s-regulatory elements for transcription factors known to have a key role in neural differentiation as well as for those that we suggest are also involved. Further, communication network analysis demonstrated that cellular interactions most frequently occurred among embryoid body (EB) stage and each cell subpopulation possessed a distinctive spectrum of ligands and receptors associated with neural differentiation which could reflect the identity of each subpopulation.\n\nConclusionsOur study provides a comprehensive and integrative study of the transcriptomics and epigenetics of human early neural differentiation, which paves the way for a deeper understanding of the regulatory mechanisms driving the differentiation of the neural lineage.

developmental biology↗

bioRxiv2018

Ancestry of the two subgenomes of maize

Maize (Zea mays ssp. mays) is not only one of the worlds most important crops, but it also is a powerful tool for studies of genetics, genomics, and cytology. The genome of maize shows the unmistakable signature of an ancient hybridization event followed by whole genome duplication (allopolyploidy), but the parents of this event have been a mystery for over a century, since studies of maize cytogenetics began. Here we show that the whole genome duplication event preceded the divergence of the entire genus Zea and its sister genus Tripsacum. One genome was donated, in whole or in part, by a plant related to the modern African genera Urelytrum and Vossia, although genomic rearrangement has been extensive. The other genome donor is less well-supported, but may have been related to the modern Rottboellia-Hemarthria clade, which is also African. Thus Zea and Tripsacum together represent a New World radiation derived from African ancestors.

plant biology↗

bioRxiv2016

Tractography-based connectomes are dominated by false-positive connections

Fiber tractography based on non-invasive diffusion imaging is at the heart of connectivity studies of the human brain. To date, the approach has not been systematically validated in ground truth studies. Based on a simulated human brain dataset with ground truth white matter tracts, we organized an open international tractography challenge, which resulted in 96 distinct submissions from 20 research groups. While most state-of-the-art algorithms reconstructed 90% of ground truth bundles to at least some extent, on average they produced four times more invalid than valid bundles. About half of the invalid bundles occurred systematically in the majority of submissions. Our results demonstrate fundamental ambiguities inherent to tract reconstruction methods based on diffusion orientation information, with critical consequences for the approach of diffusion tractography in particular and human connectivity studies in general.

neuroscience↗