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Olfactory receptor neurons are produced continuously in mammalian olfactory epithelium in vivo, but in explant cultures neurogenesis ceases abruptly. We show that in vitro neurogenesis is prolonged by fibroblast growth factors (FGFs), which act in two ways. FGFs increase the likelihood that immediate neuronal precursors (INPs) divide twice, rather than once, before generating neurons; this action requires exposure of INPs to FGFs by early G1. FGFs also cause a distinct subpopulation of explants to generate large numbers of neurons continually for at least several days. The data suggest that FGFs delay differentiation of a committed neuronal transit amplifying cell (the INP) and support proliferation or survival of a rare cell, possibly a stem cell, that acts as a progenitor to INPs.

Ankyrin repeat and SOCS box protein 15 (ASB15) is an Asb family member expressed predominantly in skeletal muscle. We have previously reported that ASB15 mRNA abundance decreases after administration of [beta]-adrenergic receptor agonists. Because [beta]-adrenergic receptor agonists are known to stimulate muscle hypertrophy, the objective of this study was to determine whether ASB15 regulates cellular processes that contribute to muscle growth. Stable myoblast [C.sub.2][C.sub.12] cells expressing full-length ASB15 (ASB15-FL) and ASB15 lacking the ankyrin repeat (ASB15-Ank) or SOCS box (ASB15-SOCS) motifs were evaluated for changes in proliferation, differentiation, protein synthesis, and protein degradation. Expression of ASB15-FL caused a delay in differentiation, followed by an increase in protein synthesis of ~34% (P < 0.05). A consistent effect of ASB15 overexpression was observed in vivo, where ectopic expression of ASB15 increased skeletal muscle fiber area (P < 0.0001) after 9 days. Expression of ASB15-SOCS altered differentiation of myoblasts, resulting in detachment of cells from culture plates. Expression of ASB15-Ank increased protein degradation by 84 h of differentiation (P < 0.05), and in vivo ectopic expression of an ASB15 construct lacking both the ankyrin repeat and SOCS box motifs decreased skeletal muscle fiber area (P < 0.0001). Together, these results suggest ASB15 participates in the regulation of protein turnover and muscle cell development by stimulating protein synthesis and regulating differentiation of muscle cells. This is the first study to demonstrate a role for an Asb family member in skeletal muscle growth. [beta]-adrenergic receptor agonist; protein turnover

The effects of a 3-week treatment with the nonsteroidal "antiestrogen" tamoxifen were determined on cortical and trabecular bone mass of the tibiae of growing male rats that had undergone unilateral sciatic neurotomy (USN). USN resulted in decreases in cortical area (-11.3%), cross-sectional area (-8.4%), and periosteal bone formation rate (-32.6%) in cortical bone, indicating that the disuse osteopenia results in a decrease in bone formation in cortical bone. USN significantly reduced the amount of trabecular bone in our metaphyseal sampling site (-75%), markedly increasing the amount of bone surface lined by osteoclasts (+65%) without affecting the surface lined by osteoblasts. These results suggest that trabecular bone disuse osteopenia is due, at least in part, to increased bone resorption. Tamoxifen treatment significantly reduced the loss of trabecular bone, restoring resorbing surface length to the control (sham-operated) animal levels. Tamoxifen treatment of sham-operated animals increased trabecular bone area and surface by 35.7% (+/- 10.5) and 41.8% (+/- 7.8), respectively, and reduced resorbing surface by 21.5% (+/- 11.6) compared with sham-operated placebo-treated rats. Tamoxifen had no significant effect on cortical bone parameters in the sham-operated group. The results indicate that tamoxifen is able to reduce the trabecular bone loss that results from USN, but has no effect on cortical bone disuse osteopenia, or on trabecular bone formation. Moreover, tamoxifen treatment of control (intact) animals inhibited the normal levels of bone resorption occurring in these rapidly growing animals. [ABSTRACT FROM AUTHOR]