Tetrapod Limb Development
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Questions and Answers

What gradient is opposed to the FGF/Wnt gradient in limb development?

  • Engrailed-1 gradient
  • Retinoic Acid gradient (correct)
  • Sonic Hedgehog gradient
  • Lmx1b gradient

What is specified by the Zone of Polarizing Activity (ZPA)?

  • Cell apoptosis
  • Dorsal-ventral axis
  • Anterior-posterior axis (correct)
  • Mesodermal differentiation

What role does Sonic Hedgehog (Shh) play in digit identity specification?

  • Stimulates apoptosis of digits
  • Specifies digit identity by preventing apoptosis (correct)
  • Determines digit length only
  • Acts solely as a mitogen for cell growth

What factor do Wnt7a and Lmx1b interact with in limb dorsal-ventral patterning?

<p>BMP signaling (A)</p> Signup and view all the answers

What might result from a Wnt7a knockout in limb development?

<p>Ventralized paws (C)</p> Signup and view all the answers

Which digit is specified independently of the Sonic Hedgehog signal?

<p>Digit 1 (D)</p> Signup and view all the answers

What is the role of apoptosis in tetrapod limb formation?

<p>To create functional joints and separate digits (D)</p> Signup and view all the answers

How does Wnt7a affect limb development?

<p>Promotes dorsal limb cell fates (C)</p> Signup and view all the answers

What is the effect of BMP proteins on interdigit mesenchyme?

<p>They trigger apoptosis. (B)</p> Signup and view all the answers

What prevents excessive cartilage formation during joint formation?

<p>Gremlin activity (A)</p> Signup and view all the answers

How does Noggin affect BMP activity in digit cartilage?

<p>It suppresses BMP activity. (D)</p> Signup and view all the answers

Which factor is implicated in the dual role of BMP in joint formation?

<p>All of the above (D)</p> Signup and view all the answers

What role does Gremlin play in the webbing of duck embryos?

<p>It inhibits BMP4. (B)</p> Signup and view all the answers

What evolutionary adaptation occurs in cetaceans regarding their limbs?

<p>Conversion of forelimb into a flipper. (C)</p> Signup and view all the answers

The lack of apoptosis in the duck's webbing is primarily due to the presence of which protein?

<p>Gremlin (B)</p> Signup and view all the answers

What leads to the elongated flippers with more phalanges in cetaceans?

<p>Extended FGF signaling. (B)</p> Signup and view all the answers

What role do Hox genes play in limb development?

<p>They provide positional cues for limb formation. (C)</p> Signup and view all the answers

Which signaling molecule is known to induce Tbx5 in limb development?

<p>Retinoic Acid (RA) (C)</p> Signup and view all the answers

How does the age of the progress zone (PZ) mesenchyme affect limb structure formation?

<p>It influences the formation of proximal-distal limb structures. (B)</p> Signup and view all the answers

What is a key function of the apical ectodermal ridge (AER) in limb development?

<p>To maintain mesenchyme in a proliferative state. (B)</p> Signup and view all the answers

What determines whether a limb is categorized as a forelimb or a hindlimb?

<p>The expression of Tbx4 or Tbx5. (C)</p> Signup and view all the answers

What happens when late progress zone mesenchyme is grafted onto an early wing bud?

<p>It produces missing intermediate structures. (D)</p> Signup and view all the answers

What effect does the expression of FGF8 in the presence of RA have on limb bud formation?

<p>It will inhibit limb bud formation. (A)</p> Signup and view all the answers

What is one of the key roles of mesenchyme in limb development?

<p>To induce and sustain the apical ectodermal ridge (AER). (D)</p> Signup and view all the answers

Which part of a tetrapod limb is referred to as the stylopod?

<p>The most proximal part exemplified by the humerus and femur (D)</p> Signup and view all the answers

What functional role does the Apical Ectodermal Ridge (AER) play during limb development?

<p>It is a thickening of ectoderm that promotes limb bud growth (A)</p> Signup and view all the answers

Which Hox genes are specifically responsible for specifying the zeugopod region in tetrapods?

<p>Hox11 (C)</p> Signup and view all the answers

What results from a knockout of Hoxa11 and Hoxd11 in mice?

<p>Reduced or absent ulna and radius in the zeugopod (C)</p> Signup and view all the answers

How is the limb field defined in embryonic development?

<p>The area where all cells are dedicated to limb development (B)</p> Signup and view all the answers

Which of the following statements about limb bud development is true?

<p>Myoblasts come from the lateral plate mesoderm (B)</p> Signup and view all the answers

What consequence does a homozygous mutation in HOXD13 have in humans?

<p>It causes fused digits and malformations in the urogenital system (D)</p> Signup and view all the answers

What is the primary function of the Zone of Polarizing Activity (ZPA) in limb development?

<p>To determine the anterior-posterior axis of the limb (C)</p> Signup and view all the answers

Flashcards

Tetrapod Limb Anatomy

Describes the structure of limbs in four-limbed vertebrates, including amphibians, reptiles, birds, and mammals.

Stylopod

The most proximal region of a tetrapod limb, closest to the body. In humans, this includes the humerus in the arm and femur in the leg.

Zeugopod

The middle region of a tetrapod limb located between the stylopod and autopod. In humans, it consists of the radius and ulna in the arm, and tibia and fibula in the leg.

Autopod

The most distal region of a tetrapod limb, furthest from the body. In humans, this includes the carpals of fingers and the tarsals of toes.

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Limb Field

The area of an embryo that contains all cells capable of forming a limb, including the surrounding tissue.

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Limb Bud

A bulge of cells at the sites of limb development, acting as a precursor to the full limb.

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Progress Zone (PZ)

A highly proliferative region of mesenchyme within the limb bud, responsible for limb bud growth.

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Apical Ectodermal Ridge (AER)

A thickening of ectoderm at the apex of the limb bud that is crucial for limb outgrowth.

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Interdigital Apoptosis

Programmed cell death between developing digits, shaping the final form of limbs. This process is regulated by BMP signaling.

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BMP's Dual Role

BMP signaling can trigger either apoptosis (cell death) or bone formation depending on the presence of other growth factors like FGFs or Wnts.

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Dickkopf (Dkk) Role in Apoptosis

Dkk protein acts as a signal to inhibit bone formation and induce apoptosis in the presence of FGFs by blocking Wnt signaling.

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Noggin's Role in Joint Formation

Noggin prevents excessive cartilage formation and ensures proper joint formation by inhibiting BMP signaling.

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Gremlin's Role in Webbed Feet

Gremlin inhibits BMP4 activity in duck webbing, preventing apoptosis and contributing to the development of webbed feet.

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Cetacean Limb Evolution

The evolution of whales, dolphins, and porpoises involved the transformation of forelimbs into flippers and the elimination of hindlimbs, driven by changes in FGF signaling.

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Evolution of Cetacean Forelimbs

Extended FGF signaling in the forelimb AER (apical ectodermal ridge) of cetacean ancestors led to elongated flippers with more phalanges, a key adaptation for aquatic life.

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Adaptive Changes in Autopod Structure

Changes in expression of BMPs and BMP inhibitors over time can lead to changes in autopod (foot and hand) structure, contributing to a variety of limb forms in different species.

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Hox Genes in Limb Development

Hox genes provide positional information, influencing limb bud alignment and location. For example, Hoxc6 gene expression marks the forelimb region.

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Tbx5 and Limb Development

Tbx5, a transcription factor induced by retinoic acid (RA), plays a key role in limb formation. It triggers expression of Fgf10 and induces epithelial-mesenchymal transitions.

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FGF10 and Limb Development

FGF10, expressed in the limb bud, promotes development and growth of the limb. Together with Tbx4 or Tbx5, it determines the type of limb (forelimb or hindlimb).

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Mesenchyme in Limb Development

The inner layer of the limb bud, which interacts with the AER and plays a critical role in determining limb type. It also induces and maintains the AER.

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PZ Graft Experiment

This experiment demonstrates how manipulating the PZ alters the limb's proximal-distal pattern. Transplanting a younger PZ to a later limb bud leads to additional structures, while an older PZ to a younger bud results in missing structures.

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AER and Retinoic Acid Roles

The Apical Ectodermal Ridge (AER) and Retinoic Acid (RA) are crucial for limb patterning. They secrete opposing gradients that influence the development of the limb.

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Zone of Polarizing Activity (ZPA)

The ZPA is a small block of mesodermal tissue at the posterior edge of the limb bud. It specifies the anterior-posterior (A-P) axis of the limb, ensuring digits develop correctly.

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Sonic Hedgehog (Shh) and ZPA

Shh, a signaling molecule, is expressed in the ZPA. It's essential for ZPA function and plays a crucial role in specifying digit identity.

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Shh Function in Digits

Shh specifies digit identity by preventing apoptosis (programmed cell death). The length of time a cell receives Shh signal influences which digit it becomes.

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Dorsal-Ventral Patterning of Limb

The dorsal-ventral (D-V) axis of the limb is determined by the overlying ectoderm. Wnt7a, expressed in the ectoderm, activates Lmx1b, which promotes dorsal cell fate.

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BMP Signaling in Limb Patterning

BMP signaling drives ventral patterning in the limb. It works in conjunction with Wnt7a to create the complete D-V axis.

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Apoptosis' Role in Digit Formation

Apoptosis, or programmed cell death, is crucial for forming separated digits and functional joints. It's a controlled process that sculpts the limb.

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Lmx1b and Ventral Limb

Lmx1b is a transcription factor essential for dorsal limb development. Mice lacking Lmx1b have ventralized paws, indicating its crucial role in dorsal patterning.

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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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BIOL 346 Developmental Biology Lesson 26 PDF

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.

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