Lecture 1 - Limb development Flashcards
What embryonic tissues give rise to the fore/hind limbs?
Ectoderm, dermatome, hypaxial portion of myotome, and somatic of lateral plate mesoderm
What gene is responsible for the timing of limb development?
Hox genes
What direction do things develop?
Proximal to distal
What gene is responsible for limb identity?
T-box
What are the three axes limbs develop in?
Proximodistal, dorsoventral, and crainocaudal
What proteins are active on the proximodistal axis?
Fgf 10, fgf 8m at AER
What is the AER?
Apical ectodermal ridge
What proteins are active on the crainocaudal axis?
Shh at ZPA
What is the ZPA?
Zone of polarizing activity
What protein/region is related to the dorsoventral axis?
Dorsal ectoderm/Wnt7a
What direction do the forelimbs rotate?
Dorsally
What direction do the hindlimbs rotate?
Venterally
What two specific things are the HOX genes responsible for?
Where the limb buds form and development at the specific location
What hox genes are responsible for different bones?
Hoxa and hoxd
How do Hox genes regulate bone growth in general?
overlap of expression
What are the two primary limb structures, in order?
Limb field - limb bud
What signal occurs during the induction of limb development?
Fgf8 induces fgf10
What is involved in the establishment of AER and ZPA centers?
Fgf10 induces Fgf8 (which induces Shh)
What are Fgf’s responsible for during AER and ZPA development?
Maintaining cell proliferation
What does Shh induce during outgrowth of the limb bud?
Fgf14
What are the main Fgf’s in early limb development?
Fgf8, 10, 14, and Shh
What are FGF10 and TBX5 responsible for together?
Induce epithelium to mesenchyme transition inducing the formation of the limb bud
What is the order of ridge development (fore vs hind)?
Forbud ridge appears 1-2 days before hindbud ridge
Where do limb buds originate from?
Ridges in ventrolateral body wall
What are the two cell layers in the limb bud?
Mesenchyme core and ectoderm cover
What are the two parts of the mesenchyme core?
Lateral plate mesoderm and paraxial mesoderm
What does the ectoderm cover become?
Epidermis of skin, nails, and hands
What does the lateral plate mesoderm become?
Cartilage, bones, and general connective tissue
What does the paraxial mesoderm become?
Somites and skeletal muscle
What region expreses Fgf10 once limb bud has formed?
Lateral plate mesoderm
What does fgf10 initiate?
AER
How does Fgf10 initiate AER?
Wnt3a and beta-catenin
What does AER express?
Fgf8 and Fgf4, while maintaining Fgf10
What interaction is the limb bud dependent on?
Limb bud mesenchyme with AER
What does AER induce?
Proliferation of limb bud mesenchyme
Where is PZ?
Area of mesenchyme proximal to AER on caudal border
What is PZ?
Progress zone
Anatomically describe AER.
thickened, specialized epithelium at tip of the limb bud on dorsoventral border
What is affecting pattern formation in dorsal-vental axis?
non-AER ectoderm
Where does D/V signaling reside?
Dorsal ectoderm w/ Wnt7a morphogen
Where do precursor muscle cells, that migrate to limb bud, come from?
Ventrolateral myotome of somite
How is motor innervation formed in limb bud?
Ventral and dorsal branches of ventral rams follow growing muscle
What axis does AER direct pattern formation for?
PD
What happens at the terminal portion of each bud?
Becomes flattened = hands and footplates
What are the three limb segments?
Stylopod, Zeugopod, and Autopod
What does the stylopod become?
arm/thigh
What does the Zeugopod become?
forearm/leg
What does the Autopod become?
hand/feet
During PD axis development what occurs with the mesenchyme?
condenses into cartilage models
What are cartilage models?
templates for long bones
What is homology?
Shared ancestry between structure, gene, etc
What is the ZPA responsible for?
Pattern formation in Cr-Cd axis.
What does the ZPA express?
RA and Shh
What does the ZPA require for stimulation?
FGF8 and Wnt7
Where does FGF8 come from?
Apical ectodermal ridge
Where does Wnt7 come?
Dorsal ectoderm
What does the Shh gradient induce?
Nested (more or less) expression of mesenchymal Hox genes.
What happens when cells leave the ZPA?
stop expressing Shh
What do Shh decedents displace and where to?
non-ZPA cells cranially
What do Shh descendants give rise to?
Ulna, digits 4, 5, and contribute to 3
What do cells give rise to via long-range Shh signaling?
Digit 2 and parts of 3
What structures come from Shh independent cells?
Humerus, radius, and digit 1
What creates the pattern of development in the PD axis?
Gradient of RA and Fgf
What creates the pattern of development in Cr-Cd axis?
Graded Shh signaling
What is hairy2?
acts as clock that controls integrated development along all axes
How does the AER progress?
Will break up and only cover emerging digital ray
How do interdigital spaces form?
Apoptosis
What is a pentadactyl limb?
“ancestral” five digit condition, digit reduction occurred over evolution
What occurs in horses in regards to digit reduction?
post-patterning changes
Digits 1 and 5 are eliminated
Digits 2 and 4 fuse (via apoptosis)
What are artiodactyls?
Catttle and swine
What occurs in artiodactyls in regards to digit reduction?
patterning changes
Digit loss and central axis shift between digits 3 and 4
What is the order of digit loss?
I, V, II, and IV
What is isometry?
Proportional relationships are preserved as size changes
What is the solution to SA being small to amount of biologically active tissue?
Being overbuilt when small
What is the solution for something growing and muscles and bones being able to keep up with growth?
Allometry
What is allometry?
Proportional changes that deviate from isometry
What does the equation for allometry consider?
A trait of interest, body size, and relationship strength of the two
What is positive allometry?
Character increases faster than body size (b>1)
What is negative allometry?
Increases slower then size or decreases with size (0>b<1)
What happens if allometry is zero?
no relationship
What is an example of positive allometry?
Skeleton mass
What is an example of negative allometry?
heart rate and basal metabolic rate
