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Questions and Answers
What gradient is opposed to the FGF/Wnt gradient in limb development?
What gradient is opposed to the FGF/Wnt gradient in limb development?
What is specified by the Zone of Polarizing Activity (ZPA)?
What is specified by the Zone of Polarizing Activity (ZPA)?
What role does Sonic Hedgehog (Shh) play in digit identity specification?
What role does Sonic Hedgehog (Shh) play in digit identity specification?
What factor do Wnt7a and Lmx1b interact with in limb dorsal-ventral patterning?
What factor do Wnt7a and Lmx1b interact with in limb dorsal-ventral patterning?
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What might result from a Wnt7a knockout in limb development?
What might result from a Wnt7a knockout in limb development?
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Which digit is specified independently of the Sonic Hedgehog signal?
Which digit is specified independently of the Sonic Hedgehog signal?
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What is the role of apoptosis in tetrapod limb formation?
What is the role of apoptosis in tetrapod limb formation?
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How does Wnt7a affect limb development?
How does Wnt7a affect limb development?
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What is the effect of BMP proteins on interdigit mesenchyme?
What is the effect of BMP proteins on interdigit mesenchyme?
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What prevents excessive cartilage formation during joint formation?
What prevents excessive cartilage formation during joint formation?
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How does Noggin affect BMP activity in digit cartilage?
How does Noggin affect BMP activity in digit cartilage?
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Which factor is implicated in the dual role of BMP in joint formation?
Which factor is implicated in the dual role of BMP in joint formation?
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What role does Gremlin play in the webbing of duck embryos?
What role does Gremlin play in the webbing of duck embryos?
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What evolutionary adaptation occurs in cetaceans regarding their limbs?
What evolutionary adaptation occurs in cetaceans regarding their limbs?
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The lack of apoptosis in the duck's webbing is primarily due to the presence of which protein?
The lack of apoptosis in the duck's webbing is primarily due to the presence of which protein?
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What leads to the elongated flippers with more phalanges in cetaceans?
What leads to the elongated flippers with more phalanges in cetaceans?
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What role do Hox genes play in limb development?
What role do Hox genes play in limb development?
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Which signaling molecule is known to induce Tbx5 in limb development?
Which signaling molecule is known to induce Tbx5 in limb development?
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How does the age of the progress zone (PZ) mesenchyme affect limb structure formation?
How does the age of the progress zone (PZ) mesenchyme affect limb structure formation?
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What is a key function of the apical ectodermal ridge (AER) in limb development?
What is a key function of the apical ectodermal ridge (AER) in limb development?
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What determines whether a limb is categorized as a forelimb or a hindlimb?
What determines whether a limb is categorized as a forelimb or a hindlimb?
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What happens when late progress zone mesenchyme is grafted onto an early wing bud?
What happens when late progress zone mesenchyme is grafted onto an early wing bud?
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What effect does the expression of FGF8 in the presence of RA have on limb bud formation?
What effect does the expression of FGF8 in the presence of RA have on limb bud formation?
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What is one of the key roles of mesenchyme in limb development?
What is one of the key roles of mesenchyme in limb development?
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Which part of a tetrapod limb is referred to as the stylopod?
Which part of a tetrapod limb is referred to as the stylopod?
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What functional role does the Apical Ectodermal Ridge (AER) play during limb development?
What functional role does the Apical Ectodermal Ridge (AER) play during limb development?
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Which Hox genes are specifically responsible for specifying the zeugopod region in tetrapods?
Which Hox genes are specifically responsible for specifying the zeugopod region in tetrapods?
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What results from a knockout of Hoxa11 and Hoxd11 in mice?
What results from a knockout of Hoxa11 and Hoxd11 in mice?
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How is the limb field defined in embryonic development?
How is the limb field defined in embryonic development?
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Which of the following statements about limb bud development is true?
Which of the following statements about limb bud development is true?
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What consequence does a homozygous mutation in HOXD13 have in humans?
What consequence does a homozygous mutation in HOXD13 have in humans?
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What is the primary function of the Zone of Polarizing Activity (ZPA) in limb development?
What is the primary function of the Zone of Polarizing Activity (ZPA) in limb development?
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Study Notes
Tetrapod Limb Development
- Tetrapods are four-limbed vertebrates (amphibians, reptiles, birds, and mammals)
- Limb anatomy has three main parts:
- Stylopod: Closest to body (humerus in arm, femur in leg)
- Zeugopod: Middle region (radius + ulna in arm, tibia + fibula in leg)
- Autopod: Furthest from body (carpals of fingers and tarsals of toes)
- Limb field: Embryonic area containing all cells capable of forming a limb
- Limb bud: Bulge of cells initiating limb development
- Progress Zone (PZ): Highly proliferative mesenchyme fueling limb bud growth
- Apical Ectodermal Ridge (AER): Thickening of ectoderm at limb bud apex
- Zone of Polarizing Activity (ZPA): Posterior cells in the progress zone that pattern the anterior-posterior axis of limbs
- Hox genes specify limb regions:
- Hox9/10: Stylopod (proximal)
- Hox11: Zeugopod (middle)
- Hox12/13: Autopod (distal)
- Hoxa11/Hoxd11 Knockout in mice leads to reduced or missing ulna and radius (zeugopod)
- Human Polysyndactyly mutation is caused by homozygous HOXD13 mutation and results in fused digits and malformations in the urogenital system
- Morphogenetic rules govern limb formation across tetrapods; limb bud grafts can induce limb formation in other species
- Limb fields are defined by predetermined mesodermal regions (somitic and lateral plate)
- Hox genes provide positional cues; mesoderm in limb regions promotes limb formation, while non-limb mesoderm represses it
Limb Field Initiation
- FGF8 and Retinoic Acid (RA) signaling are antagonistic
- RA expression, lacking FGF, allows limb bud formation
- RA induces Tbx5; Wnt2b induces FGF10
- Tbx5 induces epithelial-mesenchymal transitions
Limb Patterning
- Opposing gradients of FGF/Wnt from the AER and Retinoic Acid (RA) from the proximal flank pattern cells in the growing limb
- Treating grafts with RA or FGF/Wnt can alter limb development
ZPA
- A-P axis is specified early in limb development
- ZPA (Zone of Polarizing Activity, a small block of mesodermal tissue) specifies the A-P axis
- Shh mRNA is expressed in ZPA
- Shh is sufficient to serve ZPA's function
- Descendants of Shh-secreting cells form digits 4 and 5 and contribute to digits 2 and 3 specification
- Digit identity is influenced by the time of expressing Shh and the time of receiving paracrine Shh signal
- Digit 1 (most anterior) is specified independently of Shh signal
Dorsal-Ventral Patterning
- Wnt7a promotes dorsal limb cell fates via Lmx1b
- BMP signaling drives ventral patterning through Engrailed-1 (En1)
Apoptosis and Joint Formation
- Apoptosis is essential for forming separated digits
- Species differences influence interdigital cell death in chicks vs. ducks
- BMP signaling triggers apoptosis in the interdigital mesenchyme; Noggin protein suppresses BMP activity in digit cartilage
- BMP has a context-dependent role in joint formation; depending on the responding cells and stage of development
- Dickkopf (Dkk) mediates apoptosis in the presence of FGFs or inhibits Wnt and prevents skeleton formation
- Noggin prevents excessive cartilage formation
Evolution of the Autopod
- BMP4 induces apoptosis in chick and duck webbing
- Gremlin prevents apoptosis in duck webbing, unlike in chicks
Cetacean Limb Evolution
- Cetaceans evolved from hoofed land mammals
- Forelimbs converted into flippers; hindlimbs eliminated
- Extended FGF signaling in the forelimb AER led to elongated flippers, more phalanges and prevented interdigital apoptosis
- Early cessation of Shh signaling in hindlimb ZPA halted hindlimb development
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Description
Explore the fascinating process of limb development in tetrapods, which includes amphibians, reptiles, birds, and mammals. Learn about the key anatomical structures such as the stylopod, zeugopod, and autopod, as well as the genetic mechanisms involved in this intricate developmental process.
