Kun Liu

Vertebrate kidney tubules elongate using a planar cell polarity-dependent, rosette-based mechanism of convergent extension

Cystic kidney diseases are a global public health burden, affecting over 12 million people. Although much is known about the genetics of kidney development and disease, the cellular mechanisms driving normal kidney tubule elongation remain unclear. Here, we used in vivo imaging to show for the first time that mediolaterally oriented cell intercalation is fundamental to vertebrate kidney morphogenesis. Unexpectedly, we found that kidney tubule elongation is driven in large part by a myosin-dependent, multicellular rosette–based mechanism, previously only described in Drosophila melanogaster. In contrast to findings in Drosophila, however, non-canonical Wnt and planar cell polarity (PCP) signaling is required to control rosette topology and orientation during vertebrate kidney tubule elongation. These data resolve long-standing questions concerning the role of PCP signaling in the developing kidney and, moreover, establish rosette-based intercalation as a deeply conserved cellular engine for epithelial morphogenesis.

Rotation-Invariant HOG Descriptors Using Fourier Analysis in Polar and Spherical Coordinates

The histogram of oriented gradients (HOG) is widely used for image description and proves to be very effective. In many vision problems, rotation-invariant analysis is necessary or preferred. Popular solutions are mainly based on pose normalization or learning, neglecting some intrinsic properties of rotations. This paper presents a method to build rotation-invariant HOG descriptors using Fourier analysis in polar/spherical coordinates, which are closely related to the irreducible representation of the 2D/3D rotation groups. This is achieved by considering a gradient histogram as a continuous angular signal which can be well represented by the Fourier basis (2D) or spherical harmonics (3D). As rotation-invariance is established in an analytical way, we can avoid discretization artifacts and create a continuous mapping from the image to the feature space. In the experiments, we first show that our method outperforms the state-of-the-art in a public dataset for a car detection task in aerial images. We further use the Princeton Shape Benchmark and the SHREC 2009 Generic Shape Benchmark to demonstrate the high performance of our method for similarity measures of 3D shapes. Finally, we show an application on microscopic volumetric data.

ViBE-Z: a framework for 3D virtual colocalization analysis in zebrafish larval brains.

Precise three-dimensional (3D) mapping of a large number of gene expression patterns, neuronal types and connections to an anatomical reference helps us to understand the vertebrate brain and its development. We developed the Virtual Brain Explorer (ViBE-Z), a software that automatically maps gene expression data with cellular resolution to a 3D standard larval zebrafish (Danio rerio) brain. ViBE-Z enhances the data quality through fusion and attenuation correction of multiple confocal microscope stacks per specimen and uses a fluorescent stain of cell nuclei for image registration. It automatically detects 14 predefined anatomical landmarks for aligning new data with the reference brain. ViBE-Z performs colocalization analysis in expression databases for anatomical domains or subdomains defined by any specific pattern; here we demonstrate its utility for mapping neurons of the dopaminergic system. The ViBE-Z database, atlas and software are provided via a web interface.

Shroom3 is required downstream of FGF signalling to mediate proneuromast assembly in zebrafish

During development, morphogenetic processes require a precise coordination of cell differentiation, cell shape changes and, often, cell migration. Yet, how pattern information is used to orchestrate these different processes is still unclear. During lateral line (LL) morphogenesis, a group of cells simultaneously migrate and assemble radially organized cell clusters, termed rosettes, that prefigure LL sensory organs. This process is controlled by Fibroblast growth factor (FGF) signalling, which induces cell fate changes, cell migration and cell shape changes. However, the exact molecular mechanisms induced by FGF activation that mediate these changes on a cellular level are not known. Here, we focus on the mechanisms by which FGFs control apical constriction and rosette assembly. We show that apical constriction in the LL primordium requires the activity of non-muscle myosin. We demonstrate further that shroom3, a well-known regulator of non-muscle myosin activity, is expressed in the LL primordium and that its expression requires FGF signalling. Using gain- and loss-of-function experiments, we demonstrate that Shroom3 is the main organizer of cell shape changes during rosette assembly, probably by coordinating Rho kinase recruitment and non-muscle myosin activation. In order to quantify morphogenesis in the LL primordium in an unbiased manner, we developed a unique trainable ‘rosette detector’. We thus propose a model in which Shroom3 drives rosette assembly in the LL downstream of FGF in a Rho kinase- and non-muscle myosin-dependent manner. In conclusion, we uncovered the first mechanistic link between patterning and morphogenesis during LL sensory organ formation.

The iRoCS Toolbox – 3D analysis of the plant root apical meristem at cellular resolution

To achieve a detailed understanding of processes in biological systems, cellular features must be quantified in the three-dimensional (3D) context of cells and organs. We described use of the intrinsic root coordinate system (iRoCS) as a reference model for the root apical meristem of plants. iRoCS enables direct and quantitative comparison between the root tips of plant populations at single-cell resolution. The iRoCS Toolbox automatically fits standardized coordinates to raw 3D image data. It detects nuclei or segments cells, automatically fits the coordinate system, and groups the nuclei/cells into the roots tissue layers. The division status of each nucleus may also be determined. The only manual step required is to mark the quiescent centre. All intermediate outputs may be refined if necessary. The ability to learn the visual appearance of nuclei by example allows the iRoCS Toolbox to be easily adapted to various phenotypes. The iRoCS Toolbox is provided as an open-source software package, licensed under the GNU General Public License, to make it accessible to a broad community. To demonstrate the power of the technique, we measured subtle changes in cell division patterns caused by modified auxin flux within the Arabidopsis thaliana root apical meristem.

2D/3D rotation-invariant detection using equivariant filters and kernel weighted mapping

In many vision problems, rotation-invariant analysis is necessary or preferred. Popular solutions are mainly based on pose normalization or brute-force learning, neglecting the intrinsic properties of rotations. In this paper, we present a rotation invariant detection approach built on the equivariant filter framework, with a new model for learning the filtering behavior. The special properties of the harmonic basis, which is related to the irreducible representation of the rotation group, directly guarantees rotation invariance of the whole approach. The proposed kernel weighted mapping ensures high learning capability while respecting the invariance constraint. We demonstrate its performance on 2D object detection with in-plane rotations, and a 3D application on rotation-invariant landmark detection in microscopic volumetric data.

Amotl2a interacts with the Hippo effector Yap1 and the Wnt/β-catenin effector Lef1 to control tissue size in zebrafish

During development, proliferation must be tightly controlled for organs to reach their appropriate size. While the Hippo signaling pathway plays a major role in organ growth control, how it senses and responds to increased cell density is still unclear. In this study, we use the zebrafish lateral line primordium (LLP), a group of migrating epithelial cells that form sensory organs, to understand how tissue growth is controlled during organ formation. Loss of the cell junction-associated Motin protein Amotl2a leads to overproliferation and bigger LLP, affecting the final pattern of sensory organs. Amotl2a function in the LLP is mediated together by the Hippo pathway effector Yap1 and the Wnt/β-catenin effector Lef1. Our results implicate for the first time the Hippo pathway in size regulation in the LL system. We further provide evidence that the Hippo/Motin interaction is essential to limit tissue size during development. DOI: http://dx.doi.org/10.7554/eLife.08201.001

Optical flow guided cell segmentation and tracking in developing tissue

Cell segmentation and tracking is necessary for analyzing cell motion in time-lapse data. In this paper, we present a method which combines optical flow tracking and temporal consistency modeling to segment and track cells in time-lapse data. The method is designed for tracking cells in a dense (developing) tissue, e.g., kidney tubule in Xenopus, where cell candidates can be obtained from frame-wise segmentation methods. By modeling the temporal consistency, we can select the most probable configuration as the result of segmentation and tracking.

Hierarchy of Localized Random Forests for Video Annotation

We address the problem of annotating a video sequence with partial supervision. Given the pixel-wise annotations in the first frame, we aim to propagate these labels ideally throughout the whole video. While some labels can be propagated using optical flow, disocclusion and unreliable flow in some areas require additional cues. To this end, we propose to train localized classifiers on the annotated frame. In contrast to a global classifier, localized classifiers allow to distinguish colors that appear in both the foreground and the background but at very different locations. We design a multi-scale hierarchy of localized random forests, which collectively takes a decision. Cues from optical flow and the classifier are combined in a variational framework. The approach can deal with multiple objects in a video. We present qualitative and quantitative results on the Berkeley Motion Segmentation Dataset.

3D Rotation-Invariant Description from Tensor Operation on Spherical HOG Field

Rotation-invariant descriptions are required in many 3D volumetric image analysis tasks. The histogram-of-oriented-gradient (HOG) is widely used in 2D images and proves to be a very robust local description. This paper concentrates on how to use the HOG feature in 3D volumetric images when rotation-invariance is concerned. This is challenging because of the complexity of 3D rotations. We present a decent solution based on the spherical harmonics theory which is an effective tool for analysing 3D rotations, together with the spherical tensor operations which explore high order tensor information in spherical coordinates. The design is quite general and could be used for different applications. It achieves high scores on Princeton Shape Benchmark and SHREC 2009 Generic Shape Benchmark, and also produces promising results when applying on biological microscopy images.