Fig. 3.

Tip cells regulate multiple steps of organogenesis. Renal tip cells (with their sibling cells) stimulate tube growth by secretion of the EGF ligand Spitz to activate mitosis in neighbouring tubule cells (A). Tip cells also migrate towards chemoattractants, guiding tube outgrowth and branching morphogenesis (B). In the vasculature, tip cells guide newly sprouting vessels towards pro-angiogenic factors such as VEGF, whilst high Ret signalling activated at the tips of the kidney ureteric buds stimulates bud outgrowth. Guided tip cell migration also serves to elongate the growing tubes (C). In the insect tracheal system, tip migration towards FGF sources creates mechanical strain along the tube that induces stalk cell intercalation (SCI) and tube extension. Conversely, tip cells in insect renal systems do not lead tube outgrowth but instead anchor the tube ends to nearby muscles (D). Such anchorage antagonises forward-directed tube movement, ensuring that tubes develop a characteristic looped structure and are positioned stereotypically in the body cavity. Specialised tip cells in the vertebrate vasculature and insect tracheal systems promote tube fusion to create large interconnected tubular networks (E). In the trachea, fusion cells elongate as they migrate towards each other, before finally making contact and establishing a continuous lumen to interconnect the tubes.