Postnatal Bone Elongation of the Manus versus Pes: Analysis of the Chondrocytic Differentiation Cascade in <i>Mus musculus</i> and <i>Eptesicus fuscus</i>

Abstract

Bones elongate postnatally by endochondral ossification as cells of the cartilaginous growth plate undergo a differentiation cascade of proliferation, cellular hypertrophy and matrix synthesis. Interspecific comparisons of homologous bones elongating at different rates has been a useful approach for studying the dynamics of this process. The purpose of this study was to measure quantitative stereological parameters of growth plates of the third digit of the manus and pes of the laboratory mouse, and make comparisons to chondrocytic performance parameters in the homologous bones of the big brown bat, Eptesicus fuscus, where extremely rapid postnatal elongation of bones of the manus is associated with skeletal modifications for powered flight. Measurements were made across all zones of forelimb and hindlimb autopod growth plates by dividing each growth plate into strata of equal height (from thirteen 200-µm-high strata in the metacarpus to five 40-µm-high strata in phalangeal bones of the pes). Results indicate that all chondrocytic performance parameters known to quantitatively contribute to the elongation potential of a growth plate change together. A significant finding was that in growth plates of the chiropteran manus, final hypertrophic cell size and shape were achieved early in the zone of hypertrophy, indicating that interstitial expansion of the growth plate resulting from the incremental chondrocytic height increase in the direction of elongation was completed soon after the transition from the cessation of proliferation to the initiation of hypertrophy. This is unlike what has been reported in most mammalian growth plates previously analyzed, but is the situation in the proximal tibial growth plate of rapidly growing frogs and precocial birds. This suggests that a similar adaptation for stabilization of a rapidly elongating bone has evolved independently in three widely separated groups that have in common rapid growth in limbs to be used for early active, powered locomotion.

Mineral Distributions at the Developing Tendon Enthesis

“…2). The ∼25 µm width of the gradient region in the mouse supraspinatus enthesis is similar to the diameter of the large hypertrophic chondrocytes present early in development [43]. At the early developmental time points P7 and P10, the gradient region was often located between cells (but not always radially outward from cells), resulting in mineral on one side of the cell only (Figure 1B).…”

Artificial selection sheds light on developmental mechanisms of limb elongation

“…This effect is forelimb‐specific; by two days postnatal, metacarpal, and forelimb phalanges of the Big Brown Bat ( Eptesicus fuscus ) have thicker proliferative and hypertrophic zones with larger hypertrophic chondrocytes compared to homologous metatarsal and hindlimb phalanges (Farnum et al. ).…”

“…For example, at comparable early embryonic stages, forelimb digits in bats and mice have similar cartilage condensation size, but bat forelimb digits dramatically increase in size through enlargement of the hypertrophic zone and increases of the proliferation rate in later stages of embryogenesis (Sears et al 2006). This effect is forelimb-specific; by two days postnatal, metacarpal, and forelimb phalanges of the Big Brown Bat (Eptesicus fuscus) have thicker proliferative and hypertrophic zones with larger hypertrophic chondrocytes compared to homologous metatarsal and hindlimb phalanges (Farnum et al 2008). Chondrocyte hypertrophy also plays an important role in the dramatic metatarsal elongation in the lesser Egyptian jerboa (Cooper et al 2013), which accomplishes most of its hindlimb elongation postnatally.…”

Developmental and genetic origins of murine long bone length variation

“…Consistent with both sets of observations, Chiroptera, the bats, reprogram early limb patterning and, later, increase levels of chondrocyte hypertrophy to generate their extremely elongate long bones. (Sears et al, 2006; Ray and Capecchi, 2008; Cretekos et al, 2008; Farnum et al, 2008a, b; Hockman et al, 2008, 2009), although the precise sequence of developmental evolution has not yet been determined.…”