Muscle Development and Limbs Flashcards
The muscular system develops from
mesodermal germ layer
Types of muscle
Skeletal, smooth and cardiac
Skeletal muscle
Derived from paraxial mesoderm
Smooth muscle
Derived from visceral splanchnic mesoderm
Myotome divides into
Dorsal epaxial
Ventral hypaxial
Dorsal epaxial
Gives rise to back muscles
Ventral hypaxial
Gives rise to body wall muscles (abdomen and thorax)
Upper and Lower limb muscles
Genes MyoD and MYF-5 are essential for…
for the development of the hypaxial and epaxial muscles, respectively. Both genes are involved in the development of the abdominal and intercostal muscles
Myogenesis
Starts with the elongation of the nuclei and cell bodies of mesenchymal cells as they differentiate into myoblasts (primordial muscle cells)
Myotubes
Elongated, multinucleated, cylindrical structures formed
by the fusion of myoblasts
The beginning of Myogenesis and the induction of the myotome is regulated by…
Signaling molecules from the ventral tube (SHH), notochord (Noggin), dorsal neural tube (WNTs, NT-3), and the overlying ectoderm (BMP-4, WNT)
Myoblasts
embryonic muscle cells derived from mesenchyme
Muscle growth during development results from…
the ongoing fusion of myoblasts and myotubes
Myofilaments
develop in the cytoplasm of the myotubes during or after fusion of the myoblasts; soon after that, myofibrils and other organelles characteristic of striated muscle cells develop
Most skeletal muscle develops
before birth
Smooth Muscle Development
differentiate from splanchnic mesenchyme
surrounding the endoderm of the primordial gut
and its derivatives
The growth factor responsible for activating smooth muscle development
Serum response factor (SRF)
Smooth Muscle vessels arise from
somatic mesoderm
As smooth muscles fibers develop they receive innervation from…
Autonomic nerves
Cardiac Muscle Development
Develops from the lateral splanchnic mesoderm, which gives rise to the mesenchyme surrounding the developing heart tube
Cardiac myoblasts
differentiate from this primordial myocardium.
Cardiac muscle fibers
arise by differentiation and growth of single cells, unlike striated muscle
fibers, which develop by fusion of cells
Growth of cardiac muscle fibers results from the formation of new
myofilaments
Intercalated discs
areas of adhesion between myoblasts in which the intervening cell membrane does not disintegrate
Purkinje cells
form the conducting system of the heart
* atypical cardiac muscle cells which develop less myofibrils and are larger in diameter than typical cardiac muscle fibers
Limb Emergence
4th week
Limbs buds become visible
Limbs emergence
Parietal (somatic) layer of lateral plate mesoderm
From the bones and connective tissues of the limbs
Covered by a layer of cuboidal ectoderm
Apical ectoderm ridge
The ectoderm at the distal border of the limb thickens Also known as the undifferentiated zone
As the limb grows cells begin to differentiate
Into cartilage and muscle
Development of the limbs
proceeds proximo-distally into its three components
Three components
Stylopod
Zeugopod
Autopod
Stylopod
humerus and femur
Zeugopod
radius/ulna and tibia/fibula
Autopod
carpels, metacarpals, digit/tarsals digit/metatarsals
Limb Emergence
6th week
Limb buds become flattened to form the hand and
footplates
* Separated from the proximal segment by a circular
constriction
First hyaline cartilage models, foreshadow the
bones of the extremities
* Joints are formed in the cartilaginous condensations
Limb Emergence
8th week
- By this time a second constriction divides the proximal portion into two segments
- Fingers and toes are formed when cell death in the AER separates this ridge into five parts
Development of the upper and lower limbs is similar except …
that morphogenesis of the lower limb is approximately 1 to 2 days behind
Upper limb rotates…
90 degrees Extensor muscles lie on the lateral and posterior surface
*The thumbs lie laterally
Lower limb rotates
90 degrees medially
Placing the extensor muscles on the anterior surface
* The big toe lies medially
Somites segments for upper limb
C5-T2
Somites segments for lower limb
L2-S2
Muscles are innervated by
Ventral primary rami
Ventral primary rami
Radial n. (Dorsal segmental branches)
* Ulnar n. (Ventral branches)
* Median n. (Ventral branches)
Spinal nerves
Provide motor innervation for the
muscles
* Provide sensory innervation through the dermatomes
* Reflect the original segmental pattern of the somites and demonstrate the early association of individual spinal nerves with the derivatives of each dermomyotome
Molecular regulators of limbs
Retinoic Acid
HOXA11
HOXA13
Retinoic Acid, MEIS1
Stylopod
HOXA11
Zeugopod
HOXA13
Autopod
Growth factors of limbs
FGF10
FGF4
FGF8
Factor SHH
BMPs
HOX genes
FGF10
*Secreted by lateral plate mesoderm cells
* Initiates limbs outgrowth
FGF4 & FGF8
Secreted by the ridge
* Maintain the undifferentiated zone
Factor SHH
Contributes to the specification of the anteroposterior axis
* Digits appear in the proper order
BMPs
Regulates dorsoventral axis
HOX genes
Regulate the types and shapes of the bones of the limb
Clinical correlations
The most critical period of limb development is the 4th and 5th weeks of development.
* Mutations in HOX genes have been implicated in the development of limb anomalies
Amelia
Complete absence of one or more of the extremities
Phocomelia
Absent long bones and rudimentary hands or feet are
attached to the trunk by small, irregularly shaped bones
Syndactylyl
Two or more fingers or toes are fused
Polydactyly
Presence of extra fingers or toes
* Extra digits frequently lack proper muscle connections
