Notochord vacuoles make a rod for the vertebrate back

Notochord vacuoles make a rod for the ver tebrate back T he rod-shaped notochord is one of the fi rst prominent structures to form in the early embryo, and its evolutionary development was a key advance that allowed early chordates to grow larger and swim in the primordial oceans. In modern vertebrates, the notochord consists of two cell layers: an inner core of cells that each contain a large, fl uid-fi lled vacuole and a surrounding epithelial layer that secretes an extracellular matrix sheath (1). The vacuolated cells persist in adults as part of the intervertebral discs that connect adjacent vertebrae, yet the origin and function of the notochord vacuoles remains unknown. Ellis et al. now show that the vacuoles are lysosome-related organ-elles that control both embryonic elongation and spine morphogenesis (2). Signals from the notochord help guide embryonic patterning, but the structure also plays a mechanical role in development, acting as a skeleton before the embryo forms bones. One study using dissected notochords has suggested that osmotic swelling of the notochord vacuoles could provide a mechanical force to lengthen and straighten embryos along their anterior-posterior axis (3). This idea intrigued Michel Bagnat, from Duke University in Durham, NC, who studies how fl uid secretion contributes to tissue morphogenesis in zebrafi sh. " We're interested in fl uid pressure as a developmental force, and [notochord vacu-oles] are huge fl uid-fi lled structures, " Bagnat says. Bagnat and his colleagues Kathryn Ellis and Jennifer Bagwell fi rst examined the formation of notochord vacuoles in zebrafi sh embryos (2). In theory, these large membrane bound compartments, which occupy most of the inner notochord cells' volume, could be formed by either endocytic membrane transport or by biosynthetic vesicle traffi c through the Golgi apparatus. Ellis et al. found that blocking transport to or from the Golgi disrupted vacuole biogenesis, whereas inhibiting endocytosis had no effect on vacuole formation or maintenance. Mutations in several genes involved in sorting and transport from the Golgi to late endosomes and lysosomes—including components of the H +-ATPase that acidifi es intracellular compartments—also inhibited notochord vacuole formation. But to determine the vacuole's identity, Ellis et al. needed to fi nd a marker for the organelle. " We saw that some lysosomal markers, like LAMP1, localized to the vacuole, " Bagnat recalls. " But other lysosomal markers weren't found there. " This suggested that noto-chord vacuoles might be lysosome-related organelles …