Biology subjects

Ng, R. K.

Publications and source records attributed to Ng, R. K..

3 recordsLinked to original sources

bioRxiv2025

Reciprocal E-cadherin signaling aligns apical surfaces between neighboring epithelial tissues to complete the C. elegans digestive tract

Epithelial cells form barriers with specialized apical membranes facing the external environment or internal lumens, yet how interconnected epithelial tubular systems form from cystic epithelial primordia is poorly studied. At the boundaries of cystic epithelial primordia, apical surfaces must correctly align to yield functional connections within and between organs. Here, we use the digestive tract of the developing C. elegans embryo to define a crucial two-cell tissue, the rectal valve (vir) cells, that mediate the connection and apical alignment between the posterior intestine and the rectum. Vir cells migrate while attached to the rectal primordium to create an essential connection with the intestinal primordium and complete the digestive tract. Vir contact with the intestine, through E-cadherin signaling, is required for the intestinal apical surface to undergo a transition from a cyst with an inaccessible apical surface to an open tube competent to connect with neighboring tissues. Ablation of vir cell progenitors results in a lethal disconnection between the intestinal and rectal apical surfaces due to failure of this first step in apical accessibility. To resolve the final gap in apical continuity between the intestine and rectum, vir cells develop bipolar apical surfaces, each facing the neighboring tissue. The intestine-facing apical puncta in vir require intestinal E-cadherin signaling to form and accumulate as well as to correctly partition apical proteins within vir cells. Together these results establish E-cadherin-based signaling as the crucial factor aligning apical surfaces across primordia as epithelial cells from different germ layers form a vital connection.

developmental biology↗

bioRxiv2020

Whole-genome analysis of noncoding genetic variations identifies multigranular regulatory element perturbations associated with Hirschsprung disease

It is widely recognized that the missing heritability of many human diseases is partially due to noncoding genetic variants, but there are multiple challenges that hinder the identification of functional disease-associated noncoding variants. The number of noncoding variants can be many times of coding variants; many of them are not functional but in linkage disequilibrium with the functional ones; different variants can have epistatic effects; different variants can affect the same genes or pathways in different individuals, and some variants are related to each other not by affecting the same gene but by affecting the binding of the same upstream regulator. To overcome these difficulties, we propose a novel analysis framework that considers convergent impacts of different genetic variants on protein binding, which provides multi-granular information about disease-associated perturbations of regulatory elements, genes, and pathways. Applying it to our whole-genome sequencing data of 918 short-segment Hirschsprung disease patients and matched controls, we identify various novel genes not detected by standard single-variant and region-based tests, functionally centering on neural crest migration and development. Our framework also identifies upstream regulators whose binding is influenced by the noncoding variants. Using human neural crest cells, we confirm cell-stage-specific regulatory roles three top novel regulatory elements on our list, respectively in the RET, RASGEF1A and PIK3C2B loci. In the PIK3C2B regulatory element, we further show that a noncoding variant found only in the affects the binding of the gliogenesis regulator NFIA, with a corresponding down-regulation of multiple genes in the same topologically associating domain.

genetics↗

bioRxiv2018

Fascetto Interacting Protein (FIP) Regulates Fascetto (PRC1) to Ensure Proper Cytokinesis and Ploidy

Cell division is critical for development, organ growth, and tissue repair. The later stages of cell division include the formation of the microtubule (MT)-rich central spindle in anaphase, which is required to properly define the cell equator, guide the assembly of the acto-myosin contractile ring, and ultimately ensure complete separation and isolation of the two daughter cells via abscission. Much is known about the molecular machinery that forms the central spindle, including proteins needed to generate the antiparallel overlapping interzonal MTs. One critical protein that has garnered great attention is Protein Regulator of Cytokinesis 1 (PRC1), or Fascetto (Feo) in Drosophila, which forms a homodimer to crosslink interzonal MTs, ensuring proper central spindle formation and cytokinesis. Here, we report on a new direct protein interactor and regulator of Feo we named Fascetto Interacting Protein (FIP). Loss of FIP results in a significant reduction in Feo localization, rapid disassembly of interzonal MTs, and several cytokinesis defects. Simultaneous reduction in Feo and FIP results in tumor-like, DNA-filled masses in the brain. In aggregate our data show that FIP functions upstream of, and acts directly on, Feo to ensure fully accurate cell division.

cell biology↗