Development of the Nervous and Musculoskeletal Systems for Limb Formation 2 Flashcards
The sternum and appendicular skeleton, including the shoulder and pelvic girdles and limbs, arise from
Somatic mesoderm
Projects from the anterolateral body wall and contains mesenchyme originating from somatic mesoderm and myoblasts originating from somitic
Limb bud
The mesenchyme (somatic mesoderm) and myoblasts (somitic mesoderm) of the limb bud will differentiate to form
Connective tissues and skeletal muscles of limb respectively
The chick embryo skull shows an unstained mesenchyme membrane that will soon undergo
intramembranous ossification to form
Flat bones of the skull
Ossification continues after birth and ossification centers are completed at specific ages with varying rates between
Male and female
Mesenchymal cells of the somitic dermatome and somatic mesoderm invade tissues deep to the surface ectoderm to form the
Dermis
Forms the epidermis and epidermal derivatives like hair, nails, and sweat glands
Surface ectoderm
Form the mesenchyme that differentiates into dermis connective tissue in the face and neck
Neural crest cells
With the exception of some smooth muscle, skeletal, smooth, and cardiac muscle are all formed from the
Mesoderm
In the MSK system, skeletal muscle is derived from
Paraxial mesoderm (which differentiates into somites and then myotomes)
Myotomes contain cells that either remain in the somite region or migrate to the somatic mesoderm. These precursor muscle cells are called
Myoblasts
Forms from the migration of somitic mesoderm cells into the somatic mesoderm
Skeletal muscle
Myoblasts that do not migrate form the
Primaxial skeletal muscles of the back
Include rhomboids, levator scapulae, latissimus dorsi, intercostals, and shoulder girdle muscles
Primaxial muscles
Myoblasts that migrate to the somatic mesoderm form
Abaxial muscles of anterolateral body wall and limbs
To form the large, cylindrical, multinucleate muscle fibers/cells seen in skeletal muscle, myoblasts fuse to form a
Syncytium
Lie adjacent to skeletal muscle fibers and serve as stem cells to offer limited capacity for regeneration of damages skeletal muscle tissue
Satellite cells
Nerves and muscle cells arise from the same level
adjacent to the
Neural tube
A defect characterized by absence of the pectoralis muscles
Poland’s sequence
Can present clinically with a flattened pectoral region, a missing anterior axillary fold, and a displaced nipple
Poland’s sequence
Curves the embryo into a C-shape, with the embryo curving out towards the dorsal side
Cephalo/cranial-caudal folding of the embryo
The process where the edges of the flat embryo bend and fuse ventrally in the midline to form a cylindrically shaped embryo
Lateral folding
In lateral folding, the embryo is now a tube with two internal tubes, which are the
Gut tube and neural tube
The epidermis and underlying tissues along
the anterior body wall are derived from the ventral folding and fusion of
Ectoderm and parietal mesoderm
Also with folding of the lateral edges, the endoderm
fuses and creates the
Gut tube
The gut tube is surrounded by the
-lies between the lateral plate mesoderm layers with parietal and visceral mesoderm
Intraembryonic coelom (body cavity)
Defects can arise when the ventral body wall of the thorax, abdomen, or pelvis fail to
Fuse
Incomplete fusion in the thorax can lead to
Ectopia cordis (heart on the outside), gastroschisis (abdominal viscera on outside), and bladder extrophy (bladder on outside)
Limb buds project from the anterolateral body wall by the end of
Week 4 of development
Made up of a core of somatic mesoderm derived
mesenchyme covered by ectoderm
Limb buds
The upper limb appears first, at day 24, followed by the hind limb at
Day 28
Occurs between the fifth and eighth weeks and
involves growth, induction, apoptosis, and patterning, as described below
Differentiation of the limb buds
Surface ectoderm cells overlying the distal border of
the limb thickens into an
Apical ectodermal ridge (AER)
Acts as a signaling center that induces nearby mesenchyme (through FGF secretion) to proliferate rapidly without differentiating to maintain distal outgrowth of limb mesenchyme
The AER
The area of mesenchyme proliferation and elongation is called the
Progress zone
As the limb elongates, the AER moves distally. This distal movement allows the proximal portions of the limb to
Differentiate and develop into cartilage and bone
As the limb grows, cells near the proximal end are exposed to retinoic acid that causes them to differentiate into
Proximal bones
Digits begin formation at the DISTAL end when apoptosis occurs in the
AER
Final separation by apoptosis occurs between the webbing or rays in the interdigital spaces to form
Digits
The fusion of two or more digits that may result from incomplete apoptosis between digits
Syndactyly
Responsible for the differences in the structure of digits so that there is a “pinky side” and a “thumb side”
Zone of polarizing activity (ZPA)
Communicates with the ZPA, which is a cluster of mesenchymal cells that secrete SHH to induce differentiation of anterior-posterior patterning of digits
The AER
Dorsalizing factors that interact with ventralizing factors (such as engrailed-1) to establish the dorso-ventral axis of the limb
WNT7 and LMX1
WNT7 and LMX1 lead to a limb with an
Extensor muscle side and a flexor muscle side
Disruption of the proximal-distal development of the limbs results from loss of
FGF signaling
Disruption of the proximal-distal development of the limbs can result in
Amelia (lack of limb), Meromelia (partial lack of limb), and adactylyl (absense of digits)
Polydactyly (extra digits) and syndactylyl (fusion of digits) may be the result of
BMP or SHH disregulation or disruption
At 7 weeks, what happens to the limbs?
They rotate
Most cartilage templates of limb bones form between
5 and 12 weeks
Ossification of proximal bones in the upper limb begins in the
7th week
Ossification of proximal bones in the lower limb begins in the
8th week
Most bones show ossification by the 12th week, although ischium and pubis not until the
15th and 20th weeks
Smaller tarsal and carpal bones are not ossified until
Childhood
As the AER advances distally with mesenchymal cell proliferation, proximal mesenchymal cells differentiate into
Chondroblasts (during week 6)
Bone is vascular and replaces the avascular cartilage, which has a size limit due to reliance on
Diffusion through matrix for nutrients/waste exchange
Cartilage calcification in the diaphysis (shaft) of long bones results in poor oxygen diffusion through the
Avascular cartilage
As a result, the cartilaghe breaks down and is removed by
Osteoclasts
Blood vessels invade the diaphysis and are accompanied by
Osteoblasts
As cartilage is removed by osteoclasts, osteoblasts secrete bone matrix to form the
-occurs during prenatal development
Primary ossification center
Primary ossification centers are formed during prenatal development and are present in all long bones of limbs by the
12th week of development
At birth, diaphyses of bones are completely ossified, but the ends, the epiphyses, are still
Hyaline cartilage
Primary and secondary ossification centers form on either side of a cartilaginous
Epiphyseal growth plate
The growth plate is made of hyaline cartilage that has chondrocytes that can proliferate in response to
Growth hormone from adenohypohpysis
Located at the growth plate retain the ability to divide when stimulated by growth factors in order to increase length of long bones
Chondrocytes
Once growth is completed into adulthood (20-25 years of age), the original primary and secondary ossification centers will meet as bone fills in the growth plates to
form the
Epiphyseal line (and bone lengthening stops)
The most common form of skeletal dysplasia (1/20,000 live births) and primarily affects long bones
Achondroplasia
A gene associated with achondroplasia is
FGFR3
One of the results of achondroplasia is shortened extremities due to reduced chondrocyte proliferation at
Growth plates
Occurs while connective tissues are developing in somatic mesoderm
Muscle formation
Somitic mesoderm invades somatic mesoderm during
Week 5
Develops from ventral and dorsal condensations of somitic mesenchyme
Limb musculature
The dorsal mass forms
Extensors and supinators of upper limb
and
Extensors and abductors of lower limb
The ventral mass forms
Flexors and pronators of upper limb
and
Flexors and adductors of lower limb
Based on induction of neuroepithelium to form neurons and neuroglia of the CNS and of neural crest to form neurons and neuroglia of the PNS
Nervous System Formation
Based on origins from somites and somatic mesoderm
MSK formation
Transforms the flat trilaminar disc into a cylindrical, C-shaped embryo whose limb buds project from the anterolateral wall
Body folding
Involves orchestration of somatic mesoderm differentiation and migration of myotome myoblast cells with their innervation
Limb formation
