48 hour chick embryo serial cross section

Following activation, phosphorylation of TrkA (p-TrkA) at the axon tip or cell body can activate SHC, PI-3 kinase, and PLC-Оі1 to initiate the Ras signaling pathway ( 8). The prototypic target cellвЂ“derived neurotrophic factor NGF supports survival of developing neurons by activating one of the Trk family of receptors ( 7).

During the development of the peripheral nervous system, tissues dictate the amount and type of innervation they require by secreting neurotrophic factors, which promote neuronal survival ( 6). In addition to pain sensation, a large body of literature supports an evolutionarily conserved role of TrkA sensory nerves in organogenesis and tissue regeneration ( 5). The central mediator of bone pain is nerve growth factor (NGF), which transmits nociceptive signals either by direct activation of tropomyosin receptor kinase AвЂ“expressing (TrkA-expressing) sensory neurons or through indirect mechanisms, which enhance the response of other nociceptive pathways ( 3, 4). The most familiar role of sensory nerves is to transmit nociceptive signals, which become profoundly apparent following bone fracture. Mature bone is richly innervated by sensory nerves that infiltrate the developing axial and appendicular skeleton from the dorsal root ( 1, 2). Together, our studies demonstrate an essential role of TrkA signaling for stress fracture repair and implicate skeletal sensory nerves as an important upstream mediator of this repair process. We observed similar deficiencies in nerve regrowth and fracture healing in a mouse model of peripheral neuropathy induced by paclitaxel treatment. Temporal inhibition of TrkA catalytic activity by administration of 1NMPP1 to TrkA F592A mice significantly reduced the numbers of sensory fibers, blunted revascularization, and delayed ossification of the fracture callus. Sprouting and arborization of CGRP +TrkA + sensory nerve fibers within the reactive periosteum in NGF-enriched cellular domains were evident at time points preceding periosteal vascularization, ossification, and mineralization. Sequential histological data obtained in reporter mice subjected to fracture demonstrated a marked upregulation of NGF expression in periosteal stromal progenitors and fracture-associated macrophages. Here, we characterized the reinnervation of tissue following experimental ulnar stress fracture and assessed the impact of loss of TrkA signaling in this process.

Aside from pain sensation, little is known regarding the role of sensory innervation in bone repair. Bone is richly innervated by nerve growth factorвЂ“responsive (NGF-responsive) tropomyosin receptor kinase AвЂ“expressing (TrKa-expressing) sensory nerve fibers, which are required for osteochondral progenitor expansion during mammalian skeletal development.

48 hour chick embryo serial cross section