This review is intended for general readers who would like a basic foundation in carbohydrate structure and function, lectin biology and the implications of glycobiology in human health and disease, particularly in cancer therapeutics. These topics are among the hundreds included in the field of glycobiology and are treated here because they form the cornerstone of glycobiology or the focus of many advances in this rapidly expanding field.

Fibroblast growth factor receptor 2 (FGFR2) is a crucial regulator of bone formation during embryonic development. Both gain and loss-of-function studies in mice have shown that FGFR2 maintains a critical balance between the proliferation and differentiation of osteoprogenitor cells. We have identified de novo FGFR2 mutations in a sporadically occurring perinatal lethal skeletal dysplasia characterized by poor mineralization of the calvarium, craniosynostosis, dysmorphic facial features, prenatal teeth, hypoplastic pubis and clavicles, osteopenia, and bent long bones. Histological analysis of the long bones revealed that the growth plate contained smaller hypertrophic chondrocytes and a thickened hypercellular periosteum. Four unrelated affected individuals were found to be heterozygous for missense mutations that introduce a polar amino acid into the hydrophobic transmembrane domain of FGFR2. Using diseased chondrocytes and a cell-based assay, we determined that these mutations selectively reduced plasma-membrane levels of FGFR2 and markedly diminished the receptor's responsiveness to extracellular FGF. All together, these clinical and molecular findings are separate from previously characterized FGFR2 disorders and represent a distinct skeletal dysplasia.

Fibroblast growth factor receptor 2 (FGFR2) promotes osteoprogenitor proliferation and differentiation during bone development, yet how the receptor elicits these distinct cellular responses remains unclear. Analysis of the FGFR2-skeletal disorder bent bone dysplasia syndrome (BBDS) demonstrates that FGFR2, in addition to its canonical signaling activities at the plasma membrane, regulates bone formation from within the nucleolus. Previously, we showed that the unique FGFR2 mutations that cause BBDS reduce receptor levels at the plasma membrane and diminish responsiveness to extracellular FGF2. In this study, we find that these mutations, despite reducing canonical signaling, enhance nucleolar occupancy of FGFR2 at the ribosomal DNA (rDNA) promoter. Nucleolar FGFR2 activates rDNA transcription via interactions with FGF2 and UBF1 by de-repressing RUNX2. An increase in the nucleolar activity of FGFR2 in BBDS elevates levels of ribosomal RNA in the developing bone, consequently promoting osteoprogenitor cell proliferation and decreasing differentiation. Identifying FGFR2 as a transcriptional regulator of rDNA in bone unexpectedly reveals a nucleolar route for FGF signaling that allows for independent regulation of osteoprogenitor cell proliferation and differentiation.

We present an unusual and novel model for initial investigations of a putative role for specifically conformed glycans in cellular interactions. We have used α-and ß-amylase and α-and ß-glucosidase in dose-response experiments evaluating their effects on archenteron organization using the NIH designated sea urchin embryo model. In quantitative dose-response experiments, we show that defined activity levels of α-glucosidase and ß-amylase inhibited archenteron organization in living Lytechinus pictus gastrula embryos, whereas all concentrations of ß-glucosidase and α-amylase were without substantial effects on development. Product inhibition studies suggested that the enzymes were acting by their specific glycosidase activities and polyacrylamide gel electrophoresis suggested that there was no detectable protease contamination in the active enzyme samples. The results provide evidence for a role of glycans in sea urchin embryo cellular interactions with special reference to the possible structural conformation of these glycans based on the differential activities of the α-and ß-glycosidases.

Fibroblast Growth Factor Receptor 2 (FGFR2) promotes osteoprogenitor cell proliferation and differentiation during bone development, yet it remains unclear how the receptor couples these distinct cellular processes. Analysis of the new FGFR2‐skeletal disorder Bent Bone Dysplasia Syndrome (BBDS) suggests that the receptor, in addition to its canonical activities, regulates bone formation within the nucleolus. We previously showed that the FGFR2 mutations in BBDS reduce receptor levels at the plasma membrane and markedly diminish responsiveness to extracellular FGF2. Despite decreased canonical FGF signaling, cells with mutant FGFR2 show enhanced nucleolar localization with intracellular FGF2. The nucleolus is the site of ribosome biogenesis, and ribosome dysfunction is linked to skeletal birth defects. By employing the BBDS mutations in cultured preosteoblasts, we found that nucleolar FGFR2, along with FGF2 and the rDNA transcription factor UBF1, interacts at the rDNA promoter to promote transcription and subsequently cell proliferation. Our studies also show that nucleolar FGFR2 blocks the transcriptional repressor activities of RUNX2, the master regulator of osteoblast differentiation, at rDNA. Together this data suggest that nucleolar FGFR2 links proliferation and differentiation in preosteoblasts by regulating rRNA transcription, the rate‐limiting step in ribosome production. Grant Funding Source: Supported by NIH/NIDCR #T90DE021982 to C.L.N., MOD #5‐FY12‐166 to A.E.M., NIDCR 5 P30 DE020750‐02