Limb Development Flashcards
Describe the order of limb pattterning
Cingulum —> stylopod —> zeugopod —> auto pod
What are some examples of a stylopod
Humerus/femur
What are some examples of a zeugopod
Ulna + radius
Tibia + fibula
What are some examples of auto pods
Wrist + fingers
Ankle + toes
What does the mesenchyme core form and what layers are associated with it?
Is undifferentiated tissue
Lateral plate mesoderm and paraxial mesoderm
What does the lateral plate mesoderm form
Cartilage, bones, general CT
What does the paraxial mesoderm form
Somites, skeletal muscle
What is the ectoderm cover and what are some things it forms?
Is the outer germ layer
Out-pocketing of ventral body wall: epidermis of skin, nails, hair
Spinal nerves that will form nervous plexuses
In what fashion do elements of the limb develop
Proximal to distal fashion (humerus to distal digits)
What is the product of T-box genes
Limb identity (ie pectoral vs thoracic)
What do how genes determine?
-where limb buds will form
-what limb will develop at specific location
What does the limb field develop
Forms the limb bud
What does the limb bud develop
Develops developing limb
MUST START FROM LIMB FIELD
What transcription factors act to induce an epithelium-to-mesenchyme transition that induces the formation of the limb bud?
Fibroblast growth factors
T-box transcription factors
Describe the early development stages of the limb bud
Originates as ridges in ventrolateral body wall
FOREBUD RIDGE APPEARS FIRST then 1-2 days later, hindbud ridge appears
What 3 axes do the limbs develop along?
-proximodistal
-dorsoventral
-craniocaudal
How does the proximodistal axes work
Fibroblast growth factors acting at the apical ectodermal ridge (AER)
How does the dorsoventral axes work
Dorsal ectoderm - folding initiated by Wnt7a
How does the craniocaudal axes work
Sonic hedgehog (Shh) genes acting at the zone of polarizing activity (ZPA)
What does the apical ectodermal ridge do
-directs pattern formation on proximal-distal axis
Thickened, specialized epithelium located at the dorsoventral border of the tip of the bud
INDUCES PROLIFERATION OF LIMB BUD MESENCHYME
What happens once the limb bud acquires its terminal length
1) terminal portion of each bud becomes flattened to form hand and footplates
2) 2 constrictions divide the portion of each limb bud
-now have 3 main segments!!!
-stylopod, zeugopod, auto pod
Also, mesenchyme condenses into cartilage models - templates of future long bones
Outer shell —> general shape —> fill in details
What directs pattern formation on the dorsal-ventral axis
Non-AER ectoderm
Directs dorsal-ventral shape
Describe the dorsal-ventral development
-precursor muscle cells from ventrolateral myotome of somite migrate to limb bud
-ventral and dorsal muscle groups visible at base of each limb bud
-ventral and dorsal branches of ventral ramus follow growing muscle and provide motor inner action
-muscles are initially segmented but many fuse
-nerve branches from different segments unite into large nerves that serve the dorsal or ventral limb compartments
On the cranial-caudal axis, what directs pattern formation
Zone of polarizing activity
Describe the zone of polarizing activity (ZPA)
-area of mesenchyme on caudal border
-gives cranial-caudal identity to differentiating cells
ZPA cells express retinol acid (RA) and Shh
What does the Shh gradient induce on the cranial caudal axis
Induces nested expression of mesenchymal Hox genes
What does ZPA and Shh expression require
-input from AER
-input from dorsal ectoderm
What is the difference between apoptosis and necrosis
Programmed cell death vs traumatic cell death
Describe the final limb morphology development
-as limb development progresses, the AER breaks up and only covers the emerging digital rays
-interdigital spaces no longer have AER and can now be sculpted by apoptosis
What is homology
Existence of shared ancestors between a pair of structures, or genes, in different species
Describe the horse digit reduction
Post patterning changes
-initial limb segments are all laid in cartilage
-digits 1 and 5 are eliminated
-digits 2 and 4 reduction is the result of extensive apoptosis
Describe the cattle and swine digit reduction
Patterning changes
-digit loss and shift of central axis of foot between digits 3 and 4
describe the digit reduction of camels
Post-patterning change
Similar to horses
What is the order of digit loss?
1, 5, 2, 4
How do the final position of the limbs form?
Forelimb rotates dorsally
Hindlimb rotates ventrally
