Limb Development Flashcards
Sclerotome will give rise to ___ bones
axial
Dermomyotome will give rise to ___ ______ muscles
all skeletal
somatic mesoderm will give rise to _____ bones
appendicular
Intramembranous ossification
no cartilaginous cells are involved, forms flat bones (aka dermal or membrane bones) - facial bones, cranial vault, part of clavicle
endochondral ossification
cartilaginous cells are replaced by osseous cells, forms most bones of the body - cranial base, pharyngeal cartilages, vertebrae, thoracic cage, appendicular bones, part of clavicle
Synovial joint formation
Interzonal mesenchyme differentiates into fibroblastic tissues, which give rise to peripheral and central structures. Peripherally - articular cartilages & joint capsule. Centrally - synovial cavity, enclosed joint ligaments, menisci
Cells of skeletal myogenesis - cell origins
segmented paraxial mesoderm, unsegmented paraxial mesoderm, prechordal plate mesoderm
Cells of skeletal myogenesis - cell types
myoblasts (myofibers) & satellite cells (myofibers)
Cells of skeletal myogenesis - development waves
embryonic (myoblasts), fetal (myoblasts), and postnatal/adult (satellite cells)
Dermamyotomes differentiate into
dermatomes and myotomes
Myotomes further differentiate into
epimere and hypomere populations
Dermamyotome derivatives
dermatome, epimeres, and hypomeres
dermatome give rise to
primarily dermis of the back and neck
epimeres give rise to
intrinsic back muscles (epaxial muscles)
Hypomeres give rise to
all other skeletal muscles (hypaxial muscles)
The hypomere associates with and divides into 2 distinct populations on either side of the somatic lateral plate mesoderm -
ventral muscle mass and dorsal muscle mass
Ventral muscle mass (AKA preaxial muscle mass)
Will form the flexors, adductors, and pronators in the upper limb and in the lower limb
Muscles formed from ventral muscle mass in upper limbs
pectoralis major and minor, subclavius, anterior arm muscles, anterior/volar forearm muscles, palmar/volar hand muscles
Muscles formed from ventral muscle mass in lower limbs
medial thigh muscles, posterior thigh muscles, posterior leg muscles, plantar foot muscles, gemellus superior and inferior, obturator internus, and quadratus femoris
Dorsal muscle mass (AKA postaxial muscle mass)
will form extensors, abductors, and supinators in the upper limbs and lower limbs
Muscles formed from dorsal muscle mass in upper limbs
scapular muscles, latissimus dorsi, posterior arm muscles, posterior forearm muscles, lateral hand muscles
Muscles formed from dorsal muscle mass in lower limbs
gluteal muscles, anterior thigh muscles, biceps femoris, anterior leg muscles, lateral leg muscles, dorsal foot muscles
When and where do limb buds begin developing?
They begin forming on the ventrolateral body wall during week 4 of development
When are both limb buds fully developed?
By the end of week 8
Limb buds differentiate and grow in 3 axis -
proximal-distal axis, cranial-caudal axis, dorsal-ventral axis
Proximal-distal axis
defined along the length of the limb, such as from the shoulder to fingers or hip to toes
Cranial-caudal axis
defined along the breadth of the limb, such as from thumb to pinky or big to little toes
Dorsal-ventral axis
defined along the depth of the limb, such as from the knuckles to the palm or knee to popliteal region
What is the Apical ectodermal ridge (AER)
required for proximodistal growth, it is a thickened portion of ectoderm at the apex of the limb bud
What induces the formation of the AER?
Underlying mesenchyme
What hormone does the AER produce in order to stimulate the mesenchymal core of the limb bud to proliferate, pushing the AER away from body wall?
fetal growth factor (Fgf)
stylopod
the most proximal region and first to develop from AER, forms the arm and thigh bones
zeugopod
the intermediate region and second to develop from AER, forms the forearm and leg bones
autopod
the distal region and last to develop from AER, forms the hand and foot bones
Disruption in AER will result in
distal deletions
amelia
an anomaly where no structures of the limb formed due to early complete loss or disruption of AER
meromelia
an anomaly where the distal structures present are malformed with the most distal structures of the limb completely absent due to late complete loss or disruption of AER
cleft hands or feet (AER)
anomalies where the middle digits of a limb are absent due to late partial loss or disruption of AER
Homebox (HOX) genes
critical in determining proximodistal patterning - they direct morphological changes during development.
Absence of 1 or more HOX genes during development can lead to
middle deletions such as phocomelia - an anomaly where distal limb structures formed on proximal structures and intermediate structures are missing
Zone of polarizing activity (ZPA)
drives craniocaudal differentiation - it is a defined region along the caudal/postaxial border of the limb bud that produces sonic hedgehog (Shh)
When does Shh expression happen and what does it do?
After the hand or foot plate forms, Shh expression will happen to stimulate the formation of digits
Disruption of the ZPA can result in
aberrant digit enumeration
Polydactyly
an anomaly where there are more than 5 digits present on a limb, which can be caused by excessive Shh expression or a larger than normal ZPA
Oligodactyly or adactyly
anomalies where there are less than 5 digits present on a limb or a complete absence of digits, respectively, which can result from insufficient Shh expression or an absent ZPA
Cleft hands or feet (ZPA)
anomalies where the middle digits of a limb are absent, which can result from complex disruptions of the ZPA
what is the role of lmx1b, wnt7a, and en1?
dorsoventral patterning
Lmx1b
a specific hox gene involved in limb morphogenesis in the dorsal-ventral axis, expressed in the dorsal mesenchymal core of the limb bud, mediates the activity of Wnt7a
Wnt7a
A member of the Wnt family of genes, expressed by the dorsal ectoderm covering the limb bud, stimulates dorsalization via Lmx1b
En1
expressed by the ventral ectoderm covering the limb bud, inhibits activity of Wnt7a, thereby promoting ventralization
Nail-patella syndrome
an anomaly characterized by soft or absent nail beds in the limbs and a lack of a patella due to mutation in Lmx1b
Upper limb rotates _____ to position structures
laterally
Lower limb rotates ______ to position structures
medially
amniotic band syndrome
an anomaly similar to meromelia where the most distal structures of the limb are absent, however proximal portions of limbs are normal - occurs due to amniotic bands (scar tissue that can form in the womb) that wraps around the limb or digits during development and causing ischemic amputation
Club foot
an anomaly that is characterized by a sharp medial curvature of the foot and ankle. Caused by reduced space in the womb due to oligohydramnios or a naturally small womb with a large fetus.
Thalidomide and limb development
