A self-generated Toddler gradient guides mesodermal cell migration

The sculpting of germ layers during gastrulation relies on the coordinated migration of progenitor cells, yet the cues controlling these long-range directed movements remain largely unknown. While directional migration often relies on a chemokine gradient generated from a localized source, we find that zebrafish ventrolateral mesoderm is guided by a self-generated gradient of the initially uniformly expressed and secreted protein Toddler/ELABELA/Apela. We show that the Apelin receptor, which is specifically expressed in mesodermal cells, has a dual role during gastrulation, acting as a scavenger receptor to generate a Toddler gradient, and as a chemokine receptor to sense this guidance cue. Thus, we uncover a single receptor–based self-generated gradient as the enigmatic guidance cue that can robustly steer the directional migration of mesoderm through the complex and continuously changing environment of the gastrulating embryo

Brain-wide 3D light-field imaging of neuronal activity with speckle-enhanced resolution

A major challenge in neuroscience is to sample large-scale neuronal activity at high speed and resolution. While calcium (Ca2+) imaging allows high-resolution optical read-out of neuronal activity, it remains challenging to sample large-scale activity at high speed, as most available imaging microscopes provide a trade-off between speed and the size of the acquisition volume. One promising method that avoids the trade-off between the acquisition rate and volume size is light-field microscopy in which the full 3D profile of an object is imaged simultaneously, thereby offering high speed at the cost of reduced spatial resolution. Here we introduce speckle light-field microscopy (speckle LFM), which utilizes speckle-based structured illumination to enhance spatial resolution. Using speckle LFM we demonstrate brain-wide recording of neuronal activity in larval zebrafish at 10 Hz volume rate and at 1.4 times higher resolution compared to conventional light-field microscopy and with suppressed background fluorescence. In addition to improving resolution of spatial structure, we show that the increased resolution reduces spurious signal crosstalk between neighboring neurons. (C) 2018 Optical Society of America under the terms of the OSA Open Access Publishing Agreemen