Journal Article

A structure-based extracellular matrix expansion mechanism of fibrous tissue growth

Kalson, Nicholas S, Starborg, Tobias, Kadler, Karl E, Holmes, David F, Lu, Yinhui, Taylor, Susan H

2015

Overview

Embryonic growth occurs predominately by an increase in cell number; little is known about growth mechanisms later in development when fibrous tissues account for the bulk of adult vertebrate mass. We present a model for fibrous tissue growth based on 3D-electron microscopy of mouse tendon. We show that the number of collagen fibrils increases during embryonic development and then remains constant during postnatal growth. Embryonic growth was explained predominately by increases in fibril number and length. Postnatal growth arose predominately from increases in fibril length and diameter. A helical crimp structure was established in embryogenesis, and persisted postnatally. The data support a model where the shape and size of tendon is determined by the number and position of embryonic fibroblasts. The collagen fibrils that these cells synthesise provide a template for postnatal growth by structure-based matrix expansion. The model has important implications for growth of other fibrous tissues and fibrosis. Young animals are able to grow in a way that allows them to maintain roughly the same shape until they reach their adult size. The growth of embryos is driven by increases in cell size and number, but it is less clear how the body grows after birth. By this point, many of the cells in the body are part of tendons and other fibrous tissues, where they are surrounded by a mesh of fibres made of collagen and other proteins. These fibres provide strength to the tissue, but may also restrict its ability to grow. Tendons connect muscles to bones. They contain fibres of collagen that run along their length, which enables them to cope with very strong pulling forces. Kalson et al. used electron microscopy to generate highly detailed three-dimensional models of mouse tendons at three stages: in the embryo, at birth and six weeks later. The experiments identified two stages in tendon development. During the first stage, the number of cells and fibres across the tendon is determined in the embryo. The fibres also slightly expand in diameter and form regular waves called crimps that are important for the structural strength of the tendon. The second stage happens after birth, during which the number of cells and fibres remains constant, but the tendons continue to grow because the fibres increase in diameter and length. The cells also move to form towers of cells running along the tendon. From these observations, Kalson et al. propose that the numbers and locations of the cells and collagen fibres that determine the shape and size of tendons are established in the embryo. The collagen fibres create a framework for the continued growth of the tendon after birth. Future challenges are to understand how the number and the arrangement of cells in the tendon is determined before the collagen fibres are made, and how these cells control the number of collagen fibres that form.

• Publisher: eLife Sciences Publications Ltd,eLife Sciences Publications, Ltd
• Subject: Aging - metabolism / Animals / Animals, Newborn - embryology / Animals, Newborn - growth & development / biomechanic / Cell number / Collagen / crimp / Developmental Biology and Stem Cells / Electron microscopy / Embryo fibroblasts / Embryogenesis / Extracellular matrix / Extracellular Matrix - metabolism / Extracellular Matrix - ultrastructure / Female / fibril / Fibrillar Collagens - metabolism / Fibrillar Collagens - ultrastructure / Fibrils / Fibroblasts - cytology / Fibroblasts - metabolism / Fibroblasts - ultrastructure / Fibrosis / Male / Mice / Mice, Inbred C57BL / Microscopy, Electron, Transmission / Pregnancy / Scanning electron microscopy / tendon / Tendons / Tendons - cytology / Tendons - embryology / Tendons - growth & development / Transcription factors