TY - JOUR TI - Noise modulation in retinoic acid signaling sharpens segmental boundaries of gene expression in the embryonic zebrafish hindbrain AU - Sosnik, Julian AU - Zheng, Likun AU - Rackauckas, Christopher V AU - Digman, Michelle AU - Gratton, Enrico AU - Nie, Qing AU - Schilling, Thomas F A2 - Krumlauf, Robb VL - 5 PY - 2016 DA - 2016/04/12 SP - e14034 C1 - eLife 2016;5:e14034 DO - 10.7554/eLife.14034 UR - https://doi.org/10.7554/eLife.14034 AB - Morphogen gradients induce sharply defined domains of gene expression in a concentration-dependent manner, yet how cells interpret these signals in the face of spatial and temporal noise remains unclear. Using fluorescence lifetime imaging microscopy (FLIM) and phasor analysis to measure endogenous retinoic acid (RA) directly in vivo, we have investigated the amplitude of noise in RA signaling, and how modulation of this noise affects patterning of hindbrain segments (rhombomeres) in the zebrafish embryo. We demonstrate that RA forms a noisy gradient during critical stages of hindbrain patterning and that cells use distinct intracellular binding proteins to attenuate noise in RA levels. Increasing noise disrupts sharpening of rhombomere boundaries and proper patterning of the hindbrain. These findings reveal novel cellular mechanisms of noise regulation, which are likely to play important roles in other aspects of physiology and disease. KW - noise KW - hindbrain KW - retinoic acid KW - rhombomere KW - Danio rerio KW - morphogen JF - eLife SN - 2050-084X PB - eLife Sciences Publications, Ltd ER -