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Nerurkar, N. L.

Publications and source records attributed to Nerurkar, N. L..

5 recordsLinked to original sources

An endodermal subpopulation generates neural and mesodermal fates in the posterior chick embryo

Embryogenesis occurs through a progressive narrowing of cell fate potential, initiating with the segregation of three distinct germ layers during gastrulation. Although classically, each germ layer contributes to distinct tissue types as development proceeds, this view has been revised with the discovery of neuromesodermal progenitors (NMPs) -- a bipotent progenitor population in the posterior embryo that gives rise to traditionally ectodermal and mesodermal tissues after gastrulation has concluded. However, until now the notion of lineage restriction of the endoderm to gastrointestinal, respiratory, and endocrine tissues has largely remained intact. Here, we describe a unique subpopulation in the chick endoderm that initially lines the ventral surface of Hensens node (the amniote organizer). As posterior regression of the node ends with termination of the primitive streak, these cells undergo an FGF-dependent epithelial-to-mesenchymal transition, erasing their endodermal identity as they invade the tailbud and subsequently differentiate into a remarkably broad range of cell types including paraxial, lateral plate, and intermediate mesoderm, and to a lesser extent, notochord and neural tube. Disrupting ingression of node endoderm reduced embryonic axis elongation -- a process attributed to mesoderm -- by 50%. Through lineage barcoding, single-cell RNA sequencing, and fate mapping experiments, we conclude that the endodermal compartment of Hensens node harbors a mixed population of fate restricted and multipotent progenitor cells that give rise to clonal populations spanning traditional germ layer boundaries. These findings illustrate a surprising example of germ layer plasticity and fate convergence across distant progenitor populations during amniote development.

developmental biology↗

Elongation of the nascent avian foregut requires coordination of intrinsic and extrinsic cell behaviors

The foregut tube gives rise to the lungs and upper gastrointestinal tract, enabling vital functions of respiration and digestion. How the foregut tube forms during embryonic development has historically received considerable attention, but over the past few decades this question has primarily been addressed indirectly through studies on morphogenesis of the primitive heart tube, a closely related process. As a result, many aspects of foregut development remain unresolved. Here, we exploit the accessibility of the chick embryo to study the initial formation of the foregut tube, combining embryology with fate mapping, live imaging, and biomechanical analyses. The present study reveals that the foregut forms and elongates over a narrower time window than previously thought, and displays marked dorso-ventral and left-right asymmetries early in its development. Through tissue-specific ablation of endoderm along the anterior intestinal portal, we confirm its central biomechanical role in driving foregut morphogenesis, despite not directly contributing cells to the elongating tube. We further confirm the important role of this cell population in formation of the heart tube, with evidence that this role extends to later stages of cardiac looping as well. Together, these data reveal the need for an intricate balance between intrinsic cell behaviors and extrinsic forces for normal foregut elongation, and set the stage for future studies aimed at understanding the underlying molecular cues that coordinate this balance. GRAPHICAL ABSTRACT O_FIG O_LINKSMALLFIG WIDTH=171 HEIGHT=200 SRC="FIGDIR/small/621372v1_ufig1.gif" ALT="Figure 1"> View larger version (40K): org.highwire.dtl.DTLVardef@374c2corg.highwire.dtl.DTLVardef@69ed3aorg.highwire.dtl.DTLVardef@55823aorg.highwire.dtl.DTLVardef@1d8d4fd_HPS_FORMAT_FIGEXP M_FIG C_FIG

developmental biology↗

Application of tissue-scale tension to avian epithelia in vivo to study multiscale mechanical properties and inter-germ layer coupling

As cross-disciplinary approaches drawing from physics and mechanics have increasingly influenced our understanding of morphogenesis, the tools available to measure and perturb physical aspects of embryonic development have expanded as well. However, it remains a challenge to measure mechanical properties and apply exogenous tissue-scale forces in vivo, particularly for epithelia. Exploiting the size and accessibility of the developing chick embryo, here we describe a simple technique to quantitatively apply exogenous forces on the order of 1-100 N to the endodermal epithelium. To demonstrate the utility of this approach, we performed a series of proof-of-concept experiments that reveal fundamental and unexpected mechanical behaviors in the early chick embryo, including mechanotype heterogeneity among cells of the midgut endoderm, complex non-cell autonomous effects of actin disruption, and a high degree of mechanical coupling between the endoderm and adjacent paraxial mesoderm. To illustrate the broader utility of this method, we determined that forces on the order of 10 N are sufficient to unzip the neural tube during primary neurulation. Together, these findings provide basic insights into the mechanics of embryonic epithelia in vivo in the early avian embryo, and provide a useful tool for future investigations of how morphogenesis is influenced by mechanical factors. Graphical AbstractO_ST_ABSSummary StatementC_ST_ABS O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=101 SRC="FIGDIR/small/588089v2_ufig1.gif" ALT="Figure 1"> View larger version (59K): org.highwire.dtl.DTLVardef@7f0d90org.highwire.dtl.DTLVardef@153a4b0org.highwire.dtl.DTLVardef@614051org.highwire.dtl.DTLVardef@c5b432_HPS_FORMAT_FIGEXP M_FIG C_FIG A simple approach is devised to quantitatively apply tension to epithelia in vivo, and used to study endoderm mechanics in the deeloping chick embryo.

developmental biology↗

Elastic fibers define embryonic tissue stiffness to enable buckling morphogenesis of the small intestine

During embryonic development, tissues must possess precise material properties to ensure that cell-generated forces give rise to the stereotyped morphologies of developing organs. However, the question of how material properties are established and regulated during development remains understudied. Here, we aim to address these broader questions through the study of intestinal looping, a process by which the initially straight intestinal tube buckles into loops, permitting ordered packing within the body cavity. Looping results from elongation of the tube against the constraint of an attached tissue, the dorsal mesentery, which is elastically stretched by the elongating tube to nearly triple its length. This elastic energy storage allows the mesentery to provide stable compressive forces that ultimately buckle the tube into loops. Beginning with a transcriptomic analysis of the mesentery, we identified widespread upregulation of extracellular matrix related genes during looping, including genes related to elastic fiber deposition. Combining molecular and mechanical analyses, we conclude that elastin confers tensile stiffness to the mesentery, enabling its mechanical role in organizing the developing small intestine. These results shed light on the role of elastin as a driver of morphogenesis that extends beyond its more established role in resisting cyclic deformation in adult tissues.

developmental biology↗

Hox genes modulate physical forces to differentially shape small and large intestinal epithelia

The small and large intestines arise from a common primordial gut tube but ultimately become specialized in both form and function. While the midgut forms villi, the hindgut develops flat, brain-like sulci that resolve into heterogeneous outgrowths. Gut compartment identities are demarcated early in development via Hox genes, which are highly conserved, master regulators of spatial patterning in the embryo. Yet, how these factors trigger regional morphogenesis has remained a mystery. Combining mechanical measurements and mathematical modeling, we demonstrate that the posterior Hox gene Hoxd13 regulates biophysical phenomena that shape the hindgut lumen. We further show that Hoxd13 acts through the TGF{beta} pathway to thicken, stiffen, and promote isotropic growth of the subepithelial mesenchyme; together, these features generate hindgut surface patterns. TGF{beta}, in turn, promotes collagen deposition to affect mesenchymal geometry and growth. We thus identify a cascade of events downstream of genetic identity that direct posterior intestinal morphogenesis.

developmental biology↗