Figure 7. Model for Numb and BMP signaling in ISC/EB fate decision.

(A) During asymmetric ISC division, the basal ISC daughter transduces higher level of BMP signaling and inherits higher level of Numb activity than the apical one. Inhibition of N by BMP signaling and Numb promotes ISC fate.

(B) In numb mutant background, differential BMP signaling between the basal and apical ISC daughters is sufficient to generate differential N pathway activities to drive asymmetric fate decision.

(C) In mad mutant background, the shallow BMB activity gradient acts in conjunction with the asymmetric Numb activity to generate differential N pathway activities between the basal and apical ISC daughters to drive asymmetric fate decision.

(D) In numb mad double mutant background or in guts containing numb mutant clones and injured by bleomycin (Bleo) feeding, the shallow BMB activity gradient is often insufficient to generate asymmetric N pathway activation, leading to precocious ISC-to-EB differentiation.

BM: basement membrane. Bleo: Bleomycin; BM: basement membrane; thin line and dashed line indicate weak inhibition.