Limb development Flashcards
Each limb bud has an external layer of ______ and a core of ______ Muscle and tendon cells originate in the _____ and later migrate into the limb bud
Each limb bud has an external layer of ectoderm and a core of somatic (lateral plate) mesoderm Muscle and tendon cells originate in the somite and later migrate into the limb bud
Muscles and tendons of the limbs come from _______
Muscles and tendons of the limbs come from myoblasts (somites)
Bones, connective tissue (fascia), dermis of the limbs comes from _______
Bones, connective tissue (fascia), dermis of the limbs comes from somatic lateral plate mesoderm (all connective tissue of limb bud)
What is the Apical Ectodermal Ridge (AER)?
What induces its formation?
What factor is expressed in the AER
- APICAL ECTODERMAL RIDGE (AER)
- A distinct ridge of ectoderm at the distal end of the limb bud
- Signals in the underlying somatic mesoderm induce formation of the AER
- AER express fibroblast growth factor 8 (FGF8)
Limb buds grow from _______ axis
- ____ maintains the cells behind the AER in a proliferative, undifferentiated state
- As the AER extends further _____, some cells escape the _____ signal and start to differentiate
- Thus, the AER drives growth of the limb bud along the _______ axis
Limb buds grow from proximal to distal axis
- FGF8 maintains the cells behind the AER in a proliferative, undifferentiated state
- As the AER extends further distally, some cells escape the FGF8 signal and start to differentiate
- Thus, the AER drives growth of the limb bud along the proximal-distal axis
As limbs grow they are patterned along 3 axes:
- ________ (eg shoulder to fingertips)
- _______ (eg thumb to pinky)
- ______ (eg back of hand vs palm)
As limbs grow they are patterned along 3 axes:
- proximal-distal (eg shoulder to fingertips)
- cranial-caudal (eg thumb to pinky)
- dorsal-ventral (eg back of hand vs palm)
What are the three parts that the limb is separated into in the Proximal-distal axis?
- Stylopod
- Zeugopod
- Autopod
What are the three parts that the limb is separated into in the Proximal-distal axis?
- Stylopod
- Zeugopod
- Autopod
Proximal-distal axis
- What controls the order of differentiation
- What do we pattern first?
Proximal-distal axis
- What controls the order of differentiation
- AER (apical ectodermal ridge)
- Halted growth by cutting AER at various stages
- What do we pattern first?
- Sylopod
Proximal-distal axis:
-How do the differentiating cells know what to become?
- Each region of the limb expresses a different Hox gene code, leading to formation of different structures along the P-D axis
- Hox gene mutations lead to missing segments
What is the timing model of proximal-distal limb patterning?
- Temporal differentiation
- Cells know the order in which they are differentiating (eg count cell divisions and know what to become based on their cell division number)
What is the morphogen model of proximal-distal limb patterning
- FGFs (fibroblast growth factors) in the AER and Retinoic acid in the flank form two opposing morphogen gradients along the proximal-distal axis
Both morphogen gradients and timing mechanism are needed to pattern entire P-D axis:
- _______ pattern stylopod/zeugopod
- _______ patterns autopod
Both morphogen gradients and timing mechanism are needed to pattern entire P-D axis:
- morphogens pattern stylopod/zeugopod
- timing mechanisms patterns autopod
Morphogens in the _______ pattern the dorsal-ventral axis of the limb
Morphogens in the overlying ectoderm (developing skin) pattern the dorsal-ventral axis of the limb
Cranial Caudal axis:
- A ________ in the caudal limb bud patterns the cranial-caudal axis
- _______ is expressed by cells in [this region]
- As ____ is secreted, a gradient forms (____ caudal, ___ cranial) to pattern the axis
Cranial Caudal axis:
- A zone of polarizing activity in the caudal limb bud patterns the cranial-caudal axis
- Sonic hedgehog is expressed by cells in the ZPA
- As SHH is secreted, a gradient forms (high caudal, low cranial) to pattern the axis
- ie thumb forms where SHH is lowest (cranial)
How was the ZPA discovered?
Zone of Polarizing Activity
- Transplant of the zone of polarizing activity (ZPA) from a donor onto the cranial margin of the wing bud of host induced a mirror duplication of the cranial-caudal axis
How are individual bones established?
- Turing reaction-diffusion mechanism
- uses 2 or more interacting molecules that sort themselves into a more complex pattern
- Need both an ACTIVATOR that activates BOTH ITSELF and AN INHIBITOR
What is the Turing reaction-diffusion mechanism?
- Turing reaction-diffusion mechanism
- uses 2 or more interacting molecules that sort themselves into a more complex pattern
- Need both an ACTIVATOR that activates BOTH ITSELF and AN INHIBITOR
What 3 signaling molecules interact to create individual digits (via turing reaction-diffusion mechanism)?
Which of these drives cartilage formation?
- Wnt
- Bmp
- Sox9
- Create a repeating stripe of Sox9 which will start to form cartilage
What separates the digits?
Apoptosis
How (and when) are the limb bones formed?
- 5th-6th weeks: _______ condensations form from ________
- 6th-8th weeks: _______ (cartilage models form for each bone)
- 7th-12th weeks: ________ in most limb bones
- A few don’t appear until after birth
- 5th-6th weeks: Mesenchymal condensations form from somatic lateral plate mesoderm
- 6th-8th weeks: Chondrification (cartilage models form for each bone)
- 7th-12th weeks: Ossification centers appear in most limb bones
- A few don’t appear until after birth
What are the stages of chondrocyte development?
When do they occur?
Quiescent → proliferation → hypertrophy → death and replacement by osteoblasts
Occur during initial bone formation and at the growth plate
During each step in development, the chondrocytes express a different set of ______
During each step in development, the chondrocytes express a different set of genes
- Mutation in any of these genes depends on the particular role for that gene in bone development
- eg can cause reduced chondrocyte proliferation, premature hypertrophy, reduced differentiation
During each step in development, the chondrocytes express a different set of ______
During each step in development, the chondrocytes express a different set of genes
- Mutation in any of these genes depends on the particular role for that gene in bone development
- eg can cause reduced chondrocyte proliferation, premature hypertrophy, reduced differentiation
