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Elastic Fibers Define Embryonic Tissue Stiffness to Enable Buckling Morphogenesis of the Small Intestine

ABSTRACT: 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.

ORGANISM(S): Gallus gallus

PROVIDER: GSE237492 | GEO | 2023/07/18

REPOSITORIES: GEO

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Transcription profiling of aorta from mice underexpressing Fibulin-4 to investigate its role in elastic fibre assembly and cardio-vasuclar disease

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2007-01-01 | E-MEXP-840 | biostudies-arrayexpress

Comparative gene array analyses of severe elastic fiber defects in late embryonic and newborn mouse aorta

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2013-04-06 | E-GEOD-45821 | biostudies-arrayexpress

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2025-01-31 | GSE286272 | GEO

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Dynamic Changes in the Expressions of Elastogenesis- and Elastinolysis-Associated Genes and Remodeling of the Elastin Network in Volume-Overloaded Heart

Project description:Background: In the remodeling process of the volume-overloaded heart, the extracellular matrix (ECM) may be dynamically modified to adapt to hemodynamic stress. We investigated the expression of ECM-related genes and modification of the elastin network in the remodeling process of the left ventricles (LVs) of rats with aortocaval fistulae. Methods and Findings: Gene array analysis identified 36 upregulated and 11 downregulated ECM-related genes during evolution from the compensated to the late decompensated phase. Ingenuity Pathway Analysis identified the formation of elastic fibers as an important biological function. Real-time PCR confirmed persistent upregulation of elastogenesis-associated genes, including elastin, lysyl oxidase, lysyl oxidase like-1, fibrillin 1, fibulin 2, versican and latent transforming growth factor beta binding protein 2 at various intervals. The expression levels and enzymatic activities of potent elastases, cathepsin S and cathepsin K increased during the early phase. Immunofluorescence confocal microscopy showed that the microstructure of the elastin network was preserved during the early phase, degraded during the compensated phase, partially repaired during the early decompensated phase, and reinforced during the late decompensated phase. Assessment of elastin concentrations in the LVs showed a consistent temporal pattern throughout the course. Conclusions: In the volume-overloaded heart, upregulation of potent elastases during the early phase and persistent upregulation of elastogenesis-related genes result in early degradation followed by repair and reinforcement of the elastin network of the LV. Remodeling of the elastin network may contribute to changes in the mechanical property of the volume-overloaded heart.

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