Bidirectional Notch signaling regulates Drosophila intestinal stem cell multipotency

摘要: INTRODUCTION In the Drosophila adult midgut, multipotent intestinal stem cells (ISCs) produce two types of daughter cells: nutrient-absorbing enterocytes (ECs) and secretory enteroendocrine (ee) cells. Notch signaling between ISCs their daughters directs proper specification both these cell types. Previous work suggests that expressing high levels ligand Delta (Dl) strongly activate pathway in result differentiation into ECs. By contrast, express low Dl direct to become ee However, this unidirectional model, mechanisms regulating differential expression are poorly understood. RATIONALE During pupal midgut development, only make Therefore, we examined how made evaluated role function during developmental time window. On basis insights obtained from also asked whether similar were used by generate RESULTS The fate marker Prospero (Pros) appeared at 44 hours after formation (APF). From 96 APF, first divided asymmetrically, generating one ISC cell, followed symmetric division cells, resulting a pair asymmetric divisions, Pros was asymmetrically segregated basal process depended on Par complex. After division, expressed activated ISCs. Loss induced all differentiate whereas low-level activation blocked formation. distribution symmetric; however, polarity remained asymmetric. progeny divisions disrupted peptide hormones indicating for specification. We investigated confirmed postmitotic regulates multipotency. CONCLUSION Consistent with previous work, promoting EC differentiation. localization Pros, require signal immediate maintain Thus, is bidirectional context-dependent. has suggested remain Our data show apically located always terms polarity: Basal order divisions. provides further evidence tissue homeostasis more conserved mammalian intestine than previously thought. Inhibition mouse induces crypt base columnar loss hyperplasia, ectopic promotes leads premature formation, Because plays important roles common lymphoid progenitors making B T airway ciliated cells, it tempting speculate may regulate multipotency other