Biology subjects

Nerurkar, N.

Publications and source records attributed to Nerurkar, N..

5 recordsLinked to original sources

bioRxiv2026

Morphometric analysis reveals that the chick cranial neural tube expands as an active shell.

Embryonically, the vertebrate brain begins as an approximately uniform, fluid-filled epithelial tube that undergoes rapid volumetric expansion and regionalization to form the morphologically distinct primary brain vesicles. Hydrostatic pressure from fluid secretion into the inner lumen generates tension in the neural tube that has been implicated as a potential driver of cell proliferation during these early stages of brain development. However, a quantitatively rigorous view of 3D morphology and cellular proliferation has remained elusive. Here, we provide a standardized mapping for the mechanical and biological landscape of the developing neuroepithelium along anatomical axes. Using this 3D morphometric framework in chicken embryos, we show that localized curvature characterizes compartmental boundaries. While rapid inflation would typically be expected to stretch and thin the epithelium, we find the opposite: global expansion is coupled with significant tissue thickening, identifying the early brain as an active shell. Moreover, spatial patterns of thickness remain invariant to local curvature. Our results demonstrate a decoupling of geometry and growth, showing that spatially stable distributions of tissue thickness and mitotic activity are maintained throughout massive volumetric expansion, independent of the dramatic geometric reorganization driven by luminal pressure. We conclude that, while tension in the neuroepithelium may contribute to proliferative growth at some level, biological pre-pattern likely plays a driving role in the regionalized expansion of the early embryonic brain. Why it mattersThe embryonic brain begins as a simple fluid-filled tube that undergoes rapid and heterogeneous expansion to set up the basic organizational plan of the adult brain. Errors in this process are linked to severe neurological and congenital disorders. This work investigates the biophysical basis of expansion and regionalization of the early brain, a complex three-dimensional process driven by inflation from internal fluid pressure together with active cell behaviors that ultimately produce regionally distinct growth and curvature profiles amid a complex mechanical landscape. Graphical Abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=200 SRC="FIGDIR/small/726048v1_ufig1.gif" ALT="Figure 1"> View larger version (49K): org.highwire.dtl.DTLVardef@17c442forg.highwire.dtl.DTLVardef@1609374org.highwire.dtl.DTLVardef@170c00corg.highwire.dtl.DTLVardef@15080ad_HPS_FORMAT_FIGEXP M_FIG C_FIG

biophysics↗

bioRxiv2025

Convergent flow-mediated mesenchymal force drives embryonic foregut constriction and splitting

The transformation of a two-dimensional epithelial sheet into various three-dimensional structures is a critical process in generating the diversity of animal forms. Previous studies of epithelial folding have revealed diverse mechanisms driven by epithelium-intrinsic or -extrinsic forces. Yet little is known about the biomechanical basis of epithelial splitting, which involves extreme folding and eventually a topological transition breaking the epithelial tube. Here, we leverage tracheal-esophageal separation (TES), a critical and highly conserved morphogenetic event during tetrapod embryogenesis, as a model system for interrogating epithelial tube splitting both in vivo and ex vivo. Comparing TES in chick and mouse embryos, we identified an evolutionarily conserved, compressive force exerted by the mesenchyme surrounding the epithelium, as being necessary to drive epithelial constriction and splitting. The compressive force is mediated by localized convergent flow of mesenchymal cells towards the epithelium. We further found that Sonic hedgehog (SHH) secreted by the epithelium functions as an attractive cue for mesenchymal cells. Removal of the mesenchyme, inhibition of cell migration, or loss of SHH signaling all abrogate TES, which can be rescued by externally applied pressure. These results unveil the biomechanical basis of epithelial splitting and suggest plausible mesenchymal origins of tracheal-esophageal birth defects.

developmental biology↗

bioRxiv2024

Material Properties Of The Embryonic Small Intestine During Buckling Morphogenesis

During embryonic development, tissues undergo dramatic deformations as functional morphologies are stereotypically sculpted from simple rudiments. Formation of healthy, functional organs therefore requires tight control over the material properties of embryonic tissues during development, yet the biological basis of embryonic tissue mechanics is poorly understood. The present study investigates the mechanics of the embryonic small intestine, a tissue that is compactly organized in the body cavity by a mechanical instability during development, wherein differential elongation rates between the intestinal tube and its attached mesentery create compressive forces that buckle the tube into loops with wavelength and curvature that are tightly conserved for a given species. Focusing on the intestinal tube, we combined micromechanical testing with histologic analyses and enzymatic degradation experiments to conclude that elastic fibers closely associated with intestinal smooth muscle layers are responsible for the bending stiffness of the tube, and for establishing its pronounced mechanical anisotropy. These findings provide insights into the developmental role of elastic fibers in controlling tissue stiffness, and raise new questions on the physiologic function of elastic fibers in the intestine during adulthood. GRAPHICAL ABSTRACT O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=135 SRC="FIGDIR/small/606927v1_ufig1.gif" ALT="Figure 1"> View larger version (28K): org.highwire.dtl.DTLVardef@1bbf9d9org.highwire.dtl.DTLVardef@10428eorg.highwire.dtl.DTLVardef@181b530org.highwire.dtl.DTLVardef@9e758c_HPS_FORMAT_FIGEXP M_FIG C_FIG

developmental biology↗

bioRxiv2023

A chemo-mechanical model of endoderm movements driving elongation of the amniote hindgut

While mechanical and biochemical descriptions of development are each essential, integration of upstream morphogenic cues with downstream tissue mechanics remains understudied in many contexts during vertebrate morphogenesis. A posterior gradient of Fibroblast Growth Factor (FGF) ligands generates a contractile force gradient in the definitive endoderm, driving collective cell movements to form the hindgut. Here, we developed a two-dimensional chemo-mechanical model to investigate how mechanical properties of the endoderm and transport properties of FGF coordinately regulate this process. We began by formulating a 2-D reaction-diffusion-advection model that describes the formation of an FGF protein gradient due to posterior displacement of cells transcribing unstable Fgf8 mRNA during axis elongation, coupled with translation, diffusion, and degradation of FGF protein. This was used together with experimental measurements of FGF activity in the chick endoderm to inform a continuum model of definitive endoderm as an active viscous fluid that generates contractile stresses in proportion to FGF concentration. The model replicated key aspects of hindgut morphogenesis, confirms that heterogeneous - but isotropic - contraction is sufficient to generate large anisotropic cell movements, and provides new insight into how chemomechanical coupling across the mesoderm and endoderm coordinates hindgut elongation with outgrowth of the tailbud. Graphical Abstract O_FIG O_LINKSMALLFIG WIDTH=190 HEIGHT=200 SRC="FIGDIR/small/541363v1_ufig1.gif" ALT="Figure 1"> View larger version (49K): org.highwire.dtl.DTLVardef@abb6fborg.highwire.dtl.DTLVardef@17a297eorg.highwire.dtl.DTLVardef@13a454borg.highwire.dtl.DTLVardef@9b699d_HPS_FORMAT_FIGEXP M_FIG C_FIG Summary statementThis study employs a mathematical model to investigate the interplay between morphogen gradients and tissue mechanics in regulating the collective cell movements that drive hindgut morphogenesis in the chick embryo.

developmental biology↗

bioRxiv2021

Gene signatures and host-parasite interactions revealed by dual single-cell profiling of Plasmodium vivax liver infection

Malaria-causing P. vivax parasites can linger in the human liver for weeks to years, and then reactivate to cause recurrent blood-stage infection. While an important target for malaria eradication, little is known about the molecular features of the replicative and non-replicative states of intracellular P. vivax parasites, or the human host-cell responses to them. Here, we leverage a bioengineered human microliver platform to culture Thai clinical isolates of P. vivax in primary human hepatocytes and conduct transcriptional profiling of infected cultures. By coupling enrichment strategies with bulk and single-cell analyses, we captured both parasite and host transcripts in individual hepatocytes throughout the infection course. We defined host- and state-dependent transcriptional signatures and identified previously unappreciated populations of replicative and non-replicative parasites, sharing features with sexual transmissive forms. We found that infection suppresses transcription of key hepatocyte function genes, and that P. vivax elicits an innate immune response that can be manipulated to control infection. Our work provides an extendible framework and resource for understanding host-parasite interactions and reveals new insights into the biology of malaria dormancy and transmission.

microbiology↗