The finer points of filopodia.

The development of a single-cell zygote into an adult organism depends on highly coordinated, complex processes that control how and when cells divide, move, and change shape. The regulation of cell shape and motility is critical for the formation of functionally distinct tissues and organs and underlies a seminal event during the early development of multicellular organisms called gastrulation—when cells of different tissue types undergo large-scale rearrangements in relation to one another [1]. These processes also play an important role in the adult organism, for example, in wound healing, when fibroblasts and other cells migrate to the site of the injury to begin the process of healing [2], and in pathological situations. For instance, cancer cells migrate from their tissue of origin to populate distinct regions and organs in a process called metastasis [3], which often leads to organ failure and death in cancer patients. Cells move and change shape at the direction of signals from surrounding tissues, though the molecular mechanisms that drive these signals remain obscure. A new study reported in this issue of PLOS Biology sheds light on these processes by describing a novel molecular mechanism that links extracellular signals to cell shape changes in the nervous system [4]. The developing nervous system is a useful model for investigating such mechanisms, because a wide variety of extracellular cues direct neurons as they form the structures and functional connections that make up the central nervous system [5]–[7]. Nascent neurons often migrate from their origin in the lumen of the neural tube to populate distinct distal layers of their target tissues, resulting in the layering of neurons in the spinal cord and cerebral and cerebellar cortices. Neurons must also extend axons to specific regions of the nervous system or periphery to make synapses with the correct partners (e.g., muscles or other neurons), and they remain capable of remodeling throughout adulthood. For example, in the brain, synaptic contacts are dynamically formed, lost, and modified in size and strength in response to neuronal activity, a process referred to as synaptic plasticity [8]. These physical changes in neuronal and synaptic shape are thought to be a basis of learning and memory. Each of these cell motility events—gastrulation, neuronal migration, axon outgrowth, wound healing, and metastasis—share common cellular features. When observed in the process of development and migration, cells exhibit dynamic extension and retraction of plasma membrane protrusions called lamellipodia and filopodia that are fundamental to cell shape and motility events (Figure 1A) [9],[10]. Lamellipodia (from Latin, “thin plate protrusions”) extend dynamically from the leading edge of migrating cells and axonal growth cones, the specialized structures at the distal tips of developing axons that explore the environment and drive axon extension (Figure 1A). Filopodia (from Latin, “thread protrusions”) also emanate from the leading edges of migrating cells and growth cones, often from the edges of lamellipodia (Figure 1A). Dynamic lamellipodial protrusions are thought to generate the force required for cell and growth cone migration, whereas filopodia are thought to mediate the ability of migrating cells and growth cones to navigate their environments and sense cues as to their direction of migration and destination. Furthermore, filopodia along the shaft of dendrites are thought to be the initiating step in the formation of a new neuronal synapse, a process important in synaptic plasticity, learning, and memory. In this issue of PLoS Biology, the Research Article by Menna et al. [4] describes a signaling pathway beginning with an extracellular cue and ending with an actin-binding protein that regulates axonal filopodia formation. Figure 1 The actin cytoskeleton in lamellipodia and filopodia.