During inner ear development, Notch exhibits two modes of operation: lateral induction, which is associated with prosensory specification, and lateral inhibition, which is involved in hair cell determination. These mechanisms depend respectively on two different ligands, jagged 1 (Jag1) and delta 1 (Dl1), that rely on a common signaling cascade initiated after Notch activation. In the chicken otocyst, expression of Jag1 and the Notch target Hey1 correlates well with lateral induction, whereas both Jag1 and Dl1 are expressed during lateral inhibition, as are Notch targets Hey1 and Hes5. Here, we show that Jag1 drives lower levels of Notch activity than Dl1, which results in the differential expression of Hey1 and Hes5. In addition, Jag1 interferes with the ability of Dl1 to elicit high levels of Notch activity. Modeling the sensory epithelium when the two ligands are expressed together shows that ligand regulation, differential signaling strength and ligand competition are crucial to allow the two modes of operation and for establishing the alternate pattern of hair cells and supporting cells. Jag1, while driving lateral induction on its own, facilitates patterning by lateral inhibition in the presence of Dl1. This novel behavior emerges from Jag1 acting as a competitive inhibitor of Dl1 for Notch signaling. Both modeling and experiments show that hair cell patterning is very robust. The model suggests that autoactivation of proneural factor Atoh1, upstream of Dl1, is a fundamental component for robustness. The results stress the importance of the levels of Notch signaling and ligand competition for Notch function.

The shoot apical meristem (SAM) is responsible for the generation of all the aerial parts of plants. Given its critical role, dynamical changes in SAM activity should play a central role in the adaptation of plant architecture to the environment. Using quantitative microscopy, grafting experiments, and genetic perturbations, we connect the plant environment to the SAM by describing the molecular mechanism by which cytokinins signal the level of nutrient availability to the SAM. We show that a systemic signal of cytokinin precursors mediates the adaptation of SAM size and organogenesis rate to the availability of mineral nutrients by modulating the expression of WUSCHEL, a key regulator of stem cell homeostasis. In time-lapse experiments, we further show that this mechanism allows meristems to adapt to rapid changes in nitrate concentration, and thereby modulate their rate of organ production to the availability of mineral nutrients within a few days. Our work sheds light on the role of the stem cell regulatory network by showing that it not only maintains meristem homeostasis but also allows plants to adapt to rapid changes in the environment.Arabidopsis | shoot apical meristem | plant nutrition | plant development | cytokinin hormones P lants have evolved specific mechanisms to adapt their growth and physiology to the availability of mineral nutrients in their environment (1). Various hormones such as auxin, abscisic acid, gibberellin, and cytokinin have been shown to act in this process either locally or systemically (1). Cytokinins in particular play an essential role in plant response to nitrate, where they act as second messengers (2). For example, cytokinins promote lateral root development in areas rich in NO 3 if the overall NO 3 availability for the plant is low (3). In the shoot, cytokinins have been shown to modulate key traits such as leaf size (4, 5) and branch number (6) in response to nitrate.Cytokinins have also been shown to be critical for the maintenance of stem cell homeostasis in the shoot apical meristem (SAM). By modulating the expression of WUSCHEL (WUS), encoding for a homeodomain transcription factor expressed in the center of the meristem, cytokinins promote stem cell proliferation, thus controlling the size of the meristem and the rate of shoot organogenesis (7-10).Using grafting experiments, a recent study showed that a systemic signal of a cytokinin precursor [trans-zeatin riboside (tZR)], traveling from root to shoot through xylem, could influence the size of the vegetative meristem (11). However, it remains unclear whether cytokinin signaling can allow the SAM to respond to changes in nutrient levels in the environment. Here, we examined how a core stem cell regulator in the SAM dynamically responds to changes in mineral nutrient levels in the soil and whether systemic cytokinin signals can account for the dynamic adaptation of meristem function to nutrient levels. We used the inflorescence meristem of Arabidopsis as a model, as this structure produces all the flowers of the plant...

Multicellular development produces patterns of specialized cell types. Yet, it is often unclear how individual cells within a field of identical cells initiate the patterning process. Using live imaging, quantitative image analyses and modeling, we show that during Arabidopsis thaliana sepal development, fluctuations in the concentration of the transcription factor ATML1 pattern a field of identical epidermal cells to differentiate into giant cells interspersed between smaller cells. We find that ATML1 is expressed in all epidermal cells. However, its level fluctuates in each of these cells. If ATML1 levels surpass a threshold during the G2 phase of the cell cycle, the cell will likely enter a state of endoreduplication and become giant. Otherwise, the cell divides. Our results demonstrate a fluctuation-driven patterning mechanism for how cell fate decisions can be initiated through a random yet tightly regulated process.DOI: http://dx.doi.org/10.7554/eLife.19131.001