Strategies for tip cell selection. In the insect renal (A) and tracheal (B) systems, high levels of signalling (through the Wnt ligand Wingless in (A) and FGF in (B)) confer tip cell competence and tip cell potential is further refined by lateral inhibition through Notch/Delta. In the renal tubules, this occurs firstly within the competent cell cluster and later between the daughters of the tip cell precursor, where the outcome is biased by asymmetric inheritance of the Notch inhibitor, Numb. In the insect tracheal system, two types of tip cell are specified (terminal cell and fusion cell) according to different gene expression patterns in the progenitors (blistered in presumptive terminal and escargot in presumptive fusion cells). Conversely in mammalian kidney, cells with highest levels of Ret signalling (activated by GDNF secreted by neighbouring metanephric mesenchyme) sort out and populate the ureteric bud tips (C). Selection of DTCs in the nematode gonad is lineage dependent (D) but the asymmetric divisions of the Z1a and Z4p progenitors are biased by β-catenin/TCF signalling to specify a single DTC in each gonad arm. Image in (C) reproduced with permission from F Costantini Columbia originally published in Dev Cell doi; http://dx.doi.org/10.1016/j.devcel.2004.11.008.