Limb Development in Embryology
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Questions and Answers

What is the initial part of limb differentiation during development?

  • Circular constriction segment
  • Both proximal and distal parts simultaneously
  • Distal part of the limb
  • Proximal part of the limb (correct)
  • What process removes the interdigital tissue to create separate digits?

  • Cell division
  • Differentiation
  • Apoptosis (correct)
  • Regressive development
  • Which spinal segment levels contribute to the formation of the upper limb musculature?

  • C1-C4
  • L1-L5
  • C5-T2 (correct)
  • T3-T12
  • What structure do nails develop from during limb development?

    <p>Nail folds (A)</p> Signup and view all the answers

    What is the role of spinal nerves during limb bud development?

    <p>Without them, development stops (B)</p> Signup and view all the answers

    What initiates limb outgrowth during development?

    <p>Fibroblast growth factor (FGF) 10 (A)</p> Signup and view all the answers

    Which transcription factor is specifically responsible for the specification of the forelimb?

    <p>TBX5 (B)</p> Signup and view all the answers

    At what stage of development do limb buds first become visible?

    <p>Day 26 (D)</p> Signup and view all the answers

    Which area is covered by a layer of ectoderm during limb bud formation?

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

    What type of cells give rise to the mesenchymal core of the limb buds?

    <p>Parietal layer of lateral plate mesoderm (C)</p> Signup and view all the answers

    What is the shape of the upper limb buds at 32 days of development?

    <p>Paddle-shaped (C)</p> Signup and view all the answers

    Which genes regulate the positioning of the limbs along the craniocaudal axis?

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

    Where do the upper limb buds develop in relation to the embryo?

    <p>Opposite cervical segments (C)</p> Signup and view all the answers

    What regulates the anteroposterior axis of limb development?

    <p>Sonic hedgehog (SHH) (A)</p> Signup and view all the answers

    Which structure is essential for the proximodistal axis during limb bud development?

    <p>Apical Ectodermal Ridge (AER) (A)</p> Signup and view all the answers

    What occurs when there is misexpression of ZPA or SHH in limb development?

    <p>Formation of extra digits (polydactyly) (A)</p> Signup and view all the answers

    What component of the limb do the terms stylopod, zeugopod, and autopod refer to?

    <p>Bone segments (A)</p> Signup and view all the answers

    In the dorsoventral axis, which genes are involved in the differential patterning of bones and muscles?

    <p>Hox genes, BMP, and WNT-7 (D)</p> Signup and view all the answers

    How does the Apical Ectodermal Ridge (AER) influence limb bud growth?

    <p>By inducing cell proliferation in the mesenchyme (D)</p> Signup and view all the answers

    What is the function of Fibroblast Growth Factors (FGFs) in the limb development?

    <p>Keep cells in the progress zone proliferating (C)</p> Signup and view all the answers

    Which of the following does not relate to the limb growth along the proximodistal axis?

    <p>Regulation by sonic hedgehog (SHH) (C)</p> Signup and view all the answers

    Flashcards

    What initiates limb development?

    The process of limb development begins with the activation of mesenchymal cells from the lateral mesoderm. These cells form limb buds, which are elevations or swellings on the ventrolateral body wall.

    How are limbs positioned along the body axis?

    The HOX genes, particularly HOXB8, regulate the positioning of the limbs along the craniocaudal axis. These genes play a critical role in patterning the bones of the limbs.

    What determines the identity of forelimbs and hindlimbs?

    The transcription factor TBX5 is crucial for the specification of the forelimb, while TBX4 regulates the development of the hindlimb. These factors determine the identity of each limb.

    What factor initiates limb outgrowth?

    Fibroblast growth factor 10 (FGF10) is secreted by the lateral plate mesoderm in the limb-forming regions. This growth factor plays a critical role in initiating limb outgrowth.

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    Why are upper limb buds lower on the embryo's trunk?

    The upper limb buds appear lower on the embryo's trunk because the cranial half of the embryo develops earlier. This leads to the upper limbs developing opposite the caudal cervical segments.

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    Where do lower limb buds develop?

    The lower limb buds develop opposite the lumbar and upper sacral segments. The timing of their appearance is slightly later than the upper limb buds, making them appear slightly lower on the embryo's trunk

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    What forms the bones and connective tissues of the limb?

    The mesenchymal core of the limb bud forms the bones and connective tissues of the limb. This core is surrounded by a layer of cuboidal ectoderm.

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    What forms the limb muscles?

    The paraxial mesoderm contributes to the formation of muscles in the limbs. This mesoderm develops along the sides of the neural tube and plays a critical role in muscle formation.

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    Proximal-distal limb development

    The proximal part of the limb develops before the distal part, forming a paddle-like structure for the hand or foot, separated by a constriction.

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    Digit formation

    Fingers are formed by indentations in the hand plate, with mesenchymal condensations appearing as digital rays. Webs between fingers regress as development progresses.

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    Limb muscle origin

    Limb muscles are derived from myotomes of the somite that migrate into the limb, with specific segmental levels providing cells for specific limbs.

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    Ventral muscle mass function

    The ventral muscle mass of the limb forms the flexor and pronator groups in the upper limb and flexor and adductor groups in the lower limb.

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    Dorsal muscle mass function

    The dorsal muscle mass of the limb forms the extensor group of muscles in both the upper and lower limbs.

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    Apical Ectodermal Ridge (AER)

    The apical ectodermal ridge (AER) is a thickened area of ectoderm at the tip of each limb bud that is essential for limb development along the proximodistal axis. It secretes signaling molecules, primarily FGF, which stimulate proliferation of underlying mesenchyme, leading to outgrowth of the limb in a proximal-to-distal direction.

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    Progress Zone

    The area beneath the AER in the limb bud composed of rapidly dividing mesenchymal cells. Cells in the progress zone differentiate into cartilage and bone as they move away from the AER's FGF influence.

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    Zone of Polarizing Activity (ZPA)

    A specialized region of mesenchyme located on the posterior side of the limb bud that secretes Sonic hedgehog (Shh) signaling molecules. The ZPA controls the pattern of digits along the anteroposterior axis, ensuring the correct order of digits (thumb to little finger) from anterior to posterior.

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    Sonic Hedgehog (Shh)

    A signaling molecule secreted by the ZPA that plays a crucial role in regulating digit formation and patterning along the anteroposterior axis of the limb. Shh is essential for establishing the correct order and number of digits.

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    Proximodistal Axis of Limb Development

    The development of the limb from proximal to distal (shoulder to fingers). This process is regulated by the AER and the progress zone.

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    Anteroposterior Axis of Limb Development

    Development of the limb from anterior to posterior (thumb to little finger) and is controlled by the ZPA and its Shh signals.

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    Dorsoventral Axis of Limb Development

    The development of the dorsal/ventral (back of the hand/palm) axis of the limb. This is regulated by specific gene expression in the dorsal and ventral ectoderm.

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    Limb Components

    One of three major segments of the limb: stylopod (humerus/femur), zeugopod (radius/ulna or tibia/fibula), and autopod (hand/foot components).

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    Study Notes

    Limb Development

    • Limb development begins with mesenchymal cells activating from the lateral plate mesoderm.
    • Limb buds appear as elevations on the ventrolateral body wall around week 4 (28 days).
    • Limb buds are covered in ectoderm.
    • Upper limb buds appear around day 26/27, and lower limb buds appear a day or two later.
    • Limb buds grow larger through mesenchyme proliferation.
    • Upper limb buds develop opposite the caudal cervical segments, and lower limb buds opposite the lumbar and upper sacral segments.
    • Upper limb buds are paddle-shaped and lower limb buds are flipper-like by day 32.

    Limb Buds

    • Limb buds are formed of a mesenchymal core derived from the parietal (somatic) layer of the lateral plate mesoderm. This forms bones and connective tissue.
    • The mesenchymal core is covered in cuboidal ectoderm.
    • Upper limb buds appear opposite the lower cervical segments, and lower limb buds appear opposite the lumbar and sacral segments.

    Molecular Regulation of Limb Development

    • Limb positioning along the craniocaudal axis in the flank regions is regulated by HOX genes (HOXB8).
    • HOX genes play a critical role in patterning limb bones.
    • Forelimb specification is regulated by the transcription factor TBX5.
    • Hindlimb specification is regulated by the transcription factor TBX4.
    • Limb outgrowth is initiated by fibroblast growth factor (FGF) 10.
    • FGF10 is secreted by the lateral plate mesoderm.

    Proximodistal Axis

    • The Apical Ectodermal Ridge (AER) is crucial for limb bud development from proximal to distal.
    • AER is a thickening of ectoderm at the tip of the limb bud.
    • AER induces proliferation in underlying mesenchyme.
    • Limb buds grow distally as cells proliferate.
    • Earliest mesenchyme forms the base/proximal cells, differentiating into cartilage.
    • FGFs keep cells in the progress zone proliferating.
    • Preventing their differentiation.
    • Cells move away from FGF influence as the limb grows.
    • Decreased FGF concentration causes mesenchyme condensation and cartilage formation.

    Anteroposterior Axis

    • Anteroposterior axis is controlled by the zone of polarizing activity (ZPA).
    • Sonic hedgehog (SHH) is the master gene regulating ZPA.
    • SHH secreted by ZPA controls digit number and pattern.
    • Digits develop in a specific order (thumb on radial side).
    • Misexpression of ZPA or SHH can lead to duplication of limb structures (polydactyly).

    Dorsoventral Axis

    • Dorsoventral axis (back vs. palm) is regulated by overlapping HOX gene expression and BMP/WNT7 genes.
    • Genes control muscle pattern, orientation of joints, and epidermal differentiation.

    Limb Segmentation

    • Proximal part of the limb differentiates first, followed by the distal part.
    • Distal end flattens into a paddle-like structure (hand/foot plate).
    • Separated by proximal segments through circular constriction.
    • Second constriction divides proximal part into two segments.

    Limb Muscle

    • Limb musculature originates from somite myotomes.
    • Specific segmental levels supply muscle cells to upper and lower limbs (C5-T2 and L2-S2, respectively).
    • Muscles arranged into ventral and dorsal masses.
    • Ventral muscles become flexors and pronators in upper limbs, flexors and adductors in lower limbs.
    • Dorsal muscles become extensors.

    Limb Innervation

    • Upper limb buds develop opposite the caudal cervical spinal segments.
    • Lower limb buds develop opposite the lumbar and sacral spinal segments.
    • Spinal nerves enter limb buds early in development.

    Congenital Limb Malformations

    • Amelia: Complete absence of a limb.
    • Meromelia: Partial absence of a limb.
    • Phocomelia: A type of meromelia where long bones are absent (hands and feet attached directly to the trunk).
    • Micromelia: Limb is abnormally short, but all segments are present.
    • Brachydactyly: Short digits.
    • Syndactyly: Fused digits or toes.
    • Cleft hand/foot: A cleft between certain metacarpal/metatarsal bones; phalangeal bones may be absent.

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    Related Documents

    Limb Development PDF

    Description

    Explore the fascinating process of limb development during embryonic growth. This quiz covers the stages of limb bud formation, the specific timing of upper and lower limb bud appearances, and the molecular regulation involved in limb development. Test your knowledge on the mesenchymal and ectoderm components crucial for limb formation.

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