Skeletal Development
Skeletal tissue, which includes bone and cartilage, arises from mesenchyme derived from 3 different sources:
- somitic mesoderm
- lateral plate mesoderm
- neural crest.
The axial skeleton, which consists of skull, vertebral column, ribs and sternum is formed mostly from somite mesoderm with the exception of the facial part of the skull, which is formed from mesenchyme of neural crest origin.
The skeleton of the upper and lower appendages and their girdles is largely from lateral plate mesoderm as is the sternum.
Development of the skeleton commences in utero and continues to about age 20. Bone tissue forms by two different mechanisms which will be studied in depth in Microanatomy.
- Intramembranous ossification occurs with the development of bone tissue directly within a dense connective tissue membrane and is typical of the development of the cranial bones, mandible and clavicle, indicated by the tan color in the image.
- Endochondral ossification involves the formation of bone within a cartilaginous model of the bone. This is typical of the remainder of the skeleton, indicated in green.
Axial Skeleton
By the end of the fourth week, mesoderm occupies a position between the ectoderm and endoderm of the trilaminar embryonic disk.
The notochord forms the midline axis of the embryo.
Each somite is subdivided into sclerotome, dermatome and 2 myotomes (epimere and hypomere).
The ventromedial part of each somite (sclerotome ) under the influence of Sonic hedgehog (Shh) from the ventral neural tube and notochord, form the vertebrae and intervertebral discs.
The dorsomedial part of the somite, (myotome) becomes the epimere under the influence of Wnt proteins secreted by the dorsal neural tube. The epimere gives rise to the epaxial (above the axis) musculature, ie. deep muscles of the back (erector spinae)
The ventrolateral part of the somite (myotome) forms the hypomere under the influence of BMP4 secreted by the surface ectoderm and lateral plate mesoderm. The hypomere and lateral plate mesoderm form the muscles and skeletal elements of the body wall and limbs.
The dermatome is induced to form the dermis of the skin by neurotropin - 3 (NT-3) from the dorsal neural tube.
Somites first appear in the cranial region around day 20. By week 5, 44 pairs of somites will have formed.
This cranial to caudal, progression of somite formation is regulated by HOX genes which also determine where along the craniocaudal axis of the body the upper and lower limb buds will appear.
In this day 22 embryo, pairs of somites lie along the neural tube. Recall that the neural tube forms by fusion of the neural folds, beginning in the middle of the embryo and proceeding simultaneously in cranial and caudal directions.
At 5 weeks, roughly 44 pairs of somites can be seen through the surface ectoderm of the embryo. Viewed from the right side, they are grouped into:
- 4 occipital pairs (orange)
- 8 cervical pairs (green)
- 12 thoracic pairs (blue)
- 5 lumbar pairs (yellow)
- 5 sacral pairs (purple)
- 3-5 coccygeal pairs (pink)
The remaining somites form the vertebral column and back muscles.
Note that somites correspond to the number of vertebrae in each region of the vertebral column, except for the cervical region.
Vertebra Formation
Vertebrae form from the sclerotomes through the inductive influence of Sonic hedgehog (Shh) secreted by the notochord and ventral neural tube.
Shh, induces the cells of the sclerotome to express PAX 1, a gene that controls cartilage formation (chondrogenesis) and subsequent bone formation (osteogenesis).
Sclerotome cells migrate around the neural tube to form the vertebral arch and around the notochord to form the vertebral bodies and intervertebral discs.
In the image at right, typical lumbar vertebra is used to show the original relationships between the neural tube and notochord and the parts of the vertebra that are formed from the sclerotome.
The vertebral arch is formed by the two pedicles and laminae and spinous process. It protects the spinal cord posteriorly.
The notochord disappears within the bodies of the vertebrae, but persists in the intervertebral discs as the nucleus pulposus.
The emerging spinal nerves course in the rostral (cranial ) part of the sclerotome.
Each sclerotome splits to cranial and caudal segments at the point where the spinal nerve passes.
Subsequently, the cranial part of one sclerotome fuses with the caudal part of the sclerotome in front of it to form the vertebral bodies. By default, the intervertebral foramina are then located between the contiguous (adjacent) vertebrae.
In this image we see:
Caudal segment of the 4th occipital sclerotome (O4) fuses with the cranial part of the first cervical sclerotome (C1) to form the base of the occipital bone in the skull.
C1 spinal nerve emerges through the space between the (base of the skull) occipital bone and C1 (atlas) (red circle).
All cervical spinal nerves emerge from the intervertebral foramen superior to their correspondingly numbered vertebra ending with the C7 nerve.
C8 spinal nerve passes between the C7 and T1 vertebrae
Beginning with the T1 spinal nerve (red circle), all spinal nerves emerge from the intervertebral foramen inferior to their correspondingly numbered vertebra.
This information is useful in evaluating patients who present with sensory or motor deficits that suggest injury to a specific spinal nerve or nerves.
Cauda Equina
Cauda equina (horse's tail) is formed by the dorsal and ventral roots of lower lumbar and sacral spinal nerves.
Initially, the spinal cord and vertebral column are equal in length and the origins of all the spinal nerves are adjacent to their intervertebral foramina. As the fetus grows, the vertebral column increases in length, while the spinal cord lengthens by a much lesser degree.
As a result, the caudal (inferior) end of the spinal cord, conus medullaris, shifts upward in the vertebral canal causing elongation of thelower lumbar and sacral nerve roots creating cauda equina.
At birth, the conus medullaris is opposite the L3 vertebral level and by adulthood it has shifted upward to the level of L1 and L2.