Bone Morphogenetic Proteins (BMPs) are a group of signaling molecules that belongs to the Transforming Growth Factor-β (TGF-β) superfamily of proteins. Initially discovered for their ability to induce bone formation, BMPs are now known to play crucial roles in all organ systems. BMPs are important in embryogenesis and development, and also in maintenance of adult tissue homeostasis. Mouse knockout models of various components of the BMP signaling pathway result in embryonic lethality or marked defects, highlighting the essential functions of BMPs. In this review, we first outline the basic aspects of BMP signaling and then focus on genetically manipulated mouse knockout models that have helped elucidate the role of BMPs in development. A significant portion of this review is devoted to the prominent human pathologies associated with dysregulated BMP signaling.

SUMMARY Crosstalk and complexity within signaling pathways, and their perturbation by oncogenes, limits component-by-component approaches to understanding human disease. Network analysis of how normal and oncogenic signaling can be re-wired by drugs may provide opportunities to target tumors with high specificity and efficacy. Using targeted inhibition of oncogenic signaling pathways combined with DNA damaging chemotherapy, we report that time-staggered EGFR inhibition, but not simultaneous co-administration, dramatically sensitizes a subset of triple-negative breast cancer cells to genotoxic drugs. Systems-level analysis—using high-density time-dependent measurements of signaling networks, gene expression profiles, and cell phenotypic responses in combination with mathematical modeling— revealed an approach for altering the intrinsic state of the cell through dynamic re-wiring of oncogenic signaling pathways. This process converts these cells to a less tumorigenic state that is more susceptible to DNA damage-induced cell death by re-activation of an extrinsic apoptotic pathway whose function is suppressed in the oncogene-addicted state.

Dysphagia after anterior cervical spine surgery is a common early finding. However, it decreases significantly by 6 months. The minority of patients experience moderate or severe symptoms by 6 months after the procedure. Female gender and multiple surgical levels could be identified as risk factors for the development of postoperative dysphagia.