The Nuclear Envelope as a Signaling Node in Development and Disease

The development of a membrane-bound structure separating DNA from other cellular components was the epochal evolutionary event that gave rise to eukaryotes, possibly occurring up to 2 billion years ago. Yet, this view of the nuclear envelope as a physical barrier greatly underestimates its fundamental impact on cellular organization and complexity, much of which is only beginning to be understood. Indeed, alterations of nuclear envelope structure and protein composition are essential to many aspects of metazoan development and cellular differentiation. Mutations in genes encoding nuclear envelope proteins cause a fascinating array of diseases referred to as "nuclear envelopathies" or "laminopathies" that affect different tissues and organ systems. We review recent work on the nuclear envelope, including insights derived from the study of nuclear envelopathies. These studies are uncovering new functions for nuclear envelope proteins and underlie an emerging view of the nuclear envelope as a critical signaling node in development and disease.