Anti-SPRY1 (aa 100-200) polyclonal antibody

The temporomandibular joint is a highly conserved articulation because it promotes survival and propagation via the essential functions of mastication, communication, and routine mating success (dentofacial esthetics). The temporomandibular joint is a unique secondary joint formed between the endochondral temporal bone and the mandibular secondary condylar cartilage via Indian hedgehog and bone morphogenetic protein signaling that is closely related to ear development. A dynamic epigenetic environment is provided by Spry1 and Spry2 genetic induction of the lateral pterygoid and temporalis muscles. Mechanical loading of the condylar periosteum during fetal development produces a superficial layer of fibrocartilage that separates from the condyle to form the interposed temporomandibular joint disc. The articular surfaces of the condyle and fossa are dynamically modified periosteum that has healing and regenerative capability. This unique tissue is composed of a superficial fibrous layer (synovial surface) with an underlying proliferative (cambium) layer that produces a cushioning layer of fibrocartilage which subsequently forms bone. Prior to occlusion of the first primary (deciduous) molars at about 16 months, facial development is dominated by primary genetic mechanisms. After achieving posterior functional occlusion, biomechanics enhances temporomandibular joint maturation, and assumes control of facial growth, development and adaptation. Concurrently, hypothalamus control of musculoskeletal physiology shifts from insulin-like growth factor IGF2 to IGF1, which affects bone via muscular loading (biomechanics). Three layers of temporomandibular joint fibrocartilage are resistant to heavy functional loading, but parafunctional clenching may result in degeneration that is first manifest as trabecular sclerosis of the mandibular condyle.

Recent studies indicate that nephron progenitor cells of the embryonic kidney are arranged in a series of compartments of an increasing state of differentiation. The earliest progenitor compartment, distinguished by expression of CITED1, possesses greater capacity for renewal and differentiation than later compartments. Signaling events governing progression of nephron progenitor cells through stages of increasing differentiation are poorly understood, and their elucidation will provide key insights into normal and dysregulated nephrogenesis, as well as into regenerative processes that follow kidney injury. In this study, we found that the mouse CITED1(+) progenitor compartment is maintained in response to receptor tyrosine kinase (RTK) ligands that activate both FGF and EGF receptors. This RTK signaling function is dependent on RAS and PI3K signaling but not ERK. In vivo, RAS inactivation by expression of sprouty 1 (Spry1) in CITED1(+) nephron progenitors results in loss of characteristic molecular marker expression and in increased death of progenitor cells. Lineage tracing shows that surviving Spry1-expressing progenitor cells are impaired in their subsequent epithelial differentiation, infrequently contributing to epithelial structures. These findings demonstrate that the survival and developmental potential of cells in the earliest embryonic nephron progenitor cell compartment are dependent on FGF/EGF signaling through RAS.