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Histogenesis of the Musculo-Skeletal System

This page detailing the development of the musculo-skeletal system is relatively long and, as a result, subdivided into 3 main areas:

Myogenesis: Differentiation of Skeletal Muscle
Section through nasal septum Developing muscle fibres
The above slides are sections through the nasal septum of an embryonic mammal (i.e. through the piggie's nose!). On the left slide, observe the cartilage of the nasal septum (C) outlining the nasal passages and surrounded by mesenchyme. It is within the mesenchyme that the muscle forms from myoblasts. The myoblasts fuse with one another to form strap-like structures called myotubules. At this time, the oblong nuclei of the developing muscle still occupy a central position in the cell (as opposed to the peripheral position of the nuclei in the mature skeletal muscle cell). As the muscle continues to mature, the cells become longer and thinner and many fuse together to form the long, multinucleate muscle fibres of the mature muscle. Also, each cell will become surrounded by a thin layer of connective tissue called the endomysium. Bundles of endomysium enclosed cells will in turn become enclosed by a thicker layer of connective tissue known as the perimysium. Each perimysium enclosed bundle of muscle fibres is called a fascicle. A muscular organ (i.e. the biceps) is composed of many fascicles, which are held together by a third, very tough, layer of connective tissue called the epimysium.

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Muscle - Nerve Interaction
Motor nerve and muscle cells
This image shows vertically arranged muscle fibres (cells) and is silver stained to show very well the nerve innervating these cells. The nerve gives off many branches to the surrounding muscle cells. Each branch ends in a cluster of short terminal processes known as the motor end plate (neuromuscular junction). Each process of the motor end plate lies in a special furrow on the surface of the muscle cell membrane called a synaptic cleft. When the neurotransmitter (acetylcholine for skeletal muscle) is released from the terminal process, it initiates a sequence of events within the muscle membrane which leads to contraction of the muscle fibre. Each muscle cell receives innervation through its own motor end plate (a muscle cell spanning the whole muscle organ would have a number of motor end plates from different nerves to stimulate it across its length). The group of muscle cells receiving innervation from motor end plates arising from the same nerve (as seen here) are know as a "motor unit", as when the nerve is stimulated, all these cells will be stimulated to contract.

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Osteogenesis: Development of Bone
The formation of bone within the developing embryo can occur by two different methods. Bone tissue can form directly from mesenchymal precursors by a process called intramembranous ossification or it can form by the replacement of a temporary cartilaginous skeleton in a process called endochondral ossification.
There are three sections to this area:
Intramembranous Ossification Endochondral Ossification Endochondral Ossification (Details)


Intramembranous Ossification:
The top image shows a section through the 25-35 mm pig embryo's head. The box showing an area of the forming skull is enlarged in the second image. Membranous bone (as bone formed by intramembranous ossification is known) is formed directly from layers of mesenchymal cells without the need for a cartilage precursor. In mammals, intramembranous ossification forms many of the flat bones of the cranium (skull). In the embryo, some of the mesenchymal cells differentiate into osteoblasts and begin to secrete the bone matrix (osteoid). The matrix binds calcium to become calcified, hardening it. Later in life, the surface layers of these bones are remodelled into compact bone. Membranous bone first appears as an irregularly shaped length of tissue with many protruding spicules. The osteoblasts actively secrete bone matrix onto the surface of the spicules to form the bone. As the osteoblasts secrete matrix, they occasionally become trapped within it and are seen as cells within lacunae in the bone matrix. When this happens, the cells become known as osteocytes.
Section through 30 mm pig head
Intramembranous bone formation


Endochondral Ossification:
The top image shows the sectioned hand of a human fetus. At this time, there are no bones in the hand, but rather the structures seen where the bone will form are made of cartilage. The dense layer of mesenchyme surrounding the cartilaginous regions is known as the perichondrium (best seen in the second image). This is the area where the mesenchymal cells differentiate into chondroblasts. As with bone, when the chondroblasts become surrounded by the cartilage matrix, they change name and become known as chondrocytes. Note that there are no blood vessels with the cartilage. Cartilage is avascular (unlike bone, which has a rich blood supply).
Human fetal hand
Cartilage and perichondrium


Endochondral Ossification (Details):
This image is a low power look at a longitudinal section through the developing long bone of a mammal. The cartilage at the top of the image is being replaced by bone via endochondral ossification. As the cartilage becomes bone, the perichondrium remains, but is renamed the periosteum. This transition between cartilage and bone occurs in a number of stages, as described below:

Endochondral ossification
Zone of reserve cartilage
This is the area at the top of the image. Note the small, round chondrocytes contained within the relatively large amount of matrix (i.e. this is normal cartilage).
Zone of proliferation
Chondrocytes are flattened and arranged in columns due to successive mitotic divisions (chondrocytes are proliferating).
Zone of hypertrophy and calcification
The cartilage cells and lacunae become greatly enlarged (hypertrophied), while the matrix is reduced in size to irregular spicules that begin to show small aggregations of calcium phosphate deposits (calcification).
Zone of retrogression and ossification
The chondrocytes degenerate and die, while the calcified cartilaginous matrix is invaded by osteogenic cells and capillaries from the bone marrow cavity. Osteogenic cells gather on calcified spicules of cartilaginous matrix and begin to deposit bone matrix.
Zone of resorption
The primary spongy bone formed is remodelled to accommodate the bone marrow. This remodelling is done by osteoclasts. These are large, multinucleate cells which resorb the bone matrix. The constant laying down and resorbing of bone matrix means bones are constantly being remodelled throughout an animal's life (i.e. they are not static structures!).

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Special thanks to Hans Christoffersen for the preparation of this page.

Send comments to:
Sandra K. Ackerley (ackerley@uoguelph.ca),
Department of Zoology, University of Guelph, Guelph, Ontario, Canada N1G 2W1.