L16 E4

• Limbs


  • Crucial for movement
  • Important reservoir for fat and calcium
  • Sites of blood cell formation
• Starvation results in decalcification of bone and an increase in fat storage in the marrow cavity
• The appendicular skeleton: girdles and limbs
• Homologues


  • Femur
  • Tibia
  • Fibula
  • Tarsals
  • Metatarsals
  • Phalanges
  • Humerus
  • Radius
  • Ulna
  • Carpals
  • Metacarpals
  • Phalanges
• Analogous


  • Pectoral girdle: articulates forelimb to axial skeleton
  • Pelvic girdle: articulates hindlimb to axial skeleton
• Conserved Genes
• Limb bud development

  1. Forelimb bud initiated at most cranial point of Hox6 expression

  2. Hindlimb bud initiated at most caudal point of Hox9 expression

  3. Initiated by FGF expression at ~4 weeks (between C4-T2)

  4. Initiated by FGF expression at ~5 weeks (between L1-S2)
• Exogenous FGF initiates extra limb formation in chicken embryos
• Limb bud


  • Outgrowth of mesoderm
  • Mesoderm thickens laterally

  
• Spinal nerves follow the path of migrating dermomyotome cells
• Tbx4 and Tbx5


  1. box transcription factors that are limb-specific and determine whether a limb will be an arm or a leg

  
• Holm-Oram syndrome


  • Mutations in the Tbx5 gene can result in missing/shortened ulna, missing thumbs
• Proximal-distal patterning


  • Apical ectodermal ridge (AER) acts as a signaling center for gene expression
• AER malformations


  • Damage to the apical ectodermal ridge during development can truncate growth; result in split hands/feet
• Medial-lateral patterning


  • Zone of polarizing activity (ZPA) secretes a gradient of Sonic hedgehog (Shh) creating a medial-lateral grid
• Polydactyly


  • Mutations in Shh or translocation of ZPA can result in additional digits
• Sequential patterning genes continue to be expressed throughout development of the limb
• Digit formation


  • Apoptosis (programmed cell death) occurs between the digits resulting in distinct structures
• Syndactyly


  • Apoptotic failure leads to fused digits; most common limb deformity (1 in 2000 births)
• The limbs have separate evolutionary origins
• Fins


  • Help stabilize and propel fish through water
  • Dorsal fin
  • Pectoral fin
  • Pelvic fin
• Lobe fins – terrestriality
• Early limb girdles


  • Very robust
• Structural changes occurred in the girdles as locomotion diversified

  Frog
• Later the shoulder girdle separated from the dorsal midline
• Forelimbs


  • Adapted for versatility and mobility
• Hindlimbs


  • Adapted for stability and power
• Muscle patterning also reflects evolutionary history
• Flexor (Ventral) and Extensor (Dorsal) patterning similar in early tetrapod limbs ~295 million years ago
• Postural mechanics


  • F body mass
  • F triceps
• Crocodiles can run!...with a more erect posture
• The advantage of an erect posture = reduced resistance lever arm, better locomotor economy
• Mammalian limb positioning


  • Forelimb lateral rotation: the dorsal muscles shift caudally
  • Hindlimb medial rotation: the dorsal muscles shift cranially
• Limb rotation during embryonic development
• Blood supply and innervation match these patterns
• Developmental origins track evolution
• Evolution of human limb proportion

  • Longer legs reduce costs
  • A more erect posture makes bipedal locomotion more efficient
  • A straight limbed posture makes movement more efficient (reduced cost of transport)
• Long limbs allow for long tendons which act as springs
• Bipedality is not without costs - Human childbirth is difficult; most human births require the assistance of others
• Bipedalism freed the arms