Optical Flow on Evolving Surfaces with an Application to the Analysis of 4D Microscopy Data

We extend the concept of optical flow to a dynamic non-Euclidean setting. Optical flow is traditionally computed from a sequence of flat images. It is the purpose of this paper to introduce variational motion estimation for images that are defined on an evolving surface. Volumetric microscopy images depicting a live zebrafish embryo serve as both biological motivation and test data.Comment: The final publication is available at link.springer.co

Identifying nuclear phenotypes using semi-supervised metric learning

In systems-based approaches for studying processes such as cancer and development, identifying and characterizing individual cells within a tissue is the first step towards understanding the large-scale effects that emerge from the interactions between cells. To this end, nuclear morphology is an important phenotype to characterize the physiological and differentiated state of a cell. This study focuses on using nuclear morphology to identify cellular phenotypes in thick tissue sections imaged using 3D fluorescence microscopy. The limited label information, heterogeneous feature set describing a nucleus, and existence of sub-populations within cell-types makes this a difficult learning problem. To address these issues, a technique is presented to learn a distance metric from labeled data which is locally adaptive to account for heterogeneity in the data. Additionally, a label propagation technique is used to improve the quality of the learned metric by expanding the training set using unlabeled data. Results are presented on images of tumor stroma in breast cancer, where the framework is used to identify fibroblasts, macrophages and endothelial cells - three major stromal cells involved in carcinogenesis. © 2011 Springer-Verlag

Identifying nuclear phenotypes using semi-supervised metric learning.

In systems-based approaches for studying processes such as cancer and development, identifying and characterizing individual cells within a tissue is the first step towards understanding the large-scale effects that emerge from the interactions between cells. To this end, nuclear morphology is an important phenotype to characterize the physiological and differentiated state of a cell. This study focuses on using nuclear morphology to identify cellular phenotypes in thick tissue sections imaged using 3D fluorescence microscopy. The limited label information, heterogeneous feature set describing a nucleus, and existence of subpopulations within cell-types makes this a difficult learning problem. To address these issues, a technique is presented to learn a distance metric from labeled data which is locally adaptive to account for heterogeneity in the data. Additionally, a label propagation technique is used to improve the quality of the learned metric by expanding the training set using unlabeled data. Results are presented on images of tumor stroma in breast cancer, where the framework is used to identify fibroblasts, macrophages and endothelial cells--three major stromal cells involved in carcinogenesis

Bmper is required for morphogenesis of the anterior and posterior semicircular canal ducts in the developing zebrafish inner ear

BMP signalling is known to have a conserved function in development of the semicircular canal system of the vertebrate inner ear, but its regulation, target genes and effects on cell behaviour during otic morphogenesis are not fully understood. We have characterised the effects of mutations in the zebrafish gene bmper, which codes for a regulator of BMP signalling with both pro- and anti-BMP roles in different developmental contexts. The inner ears of bmper mutant embryos develop with truncations of the anterior and posterior semicircular canal ducts. To image the developing ear in live embryos, we have exploited a new transgenic line, Tg(smad6b:EGFP), which exhibits strong GFP expression in the otic epithelium. Morphometric analysis indicates defects in the bmper mutant ear from early stages of semicircular canal formation, correlating with a specific reduction in BMP signalling activity and specific loss of dlx5a expression in dorsal otic epithelium. Subsequent changes to cell shape occur at the truncation site and the dorsolateral septum. The bmper mutations that we describe are adult viable; truncation of the anterior and posterior semicircular canal ducts persists into adulthood. Our results argue against a major role for Bmper in specification of the pre-placodal region, induction of the otic placode, or development of the neural crest, processes in which Bmper function has previously been implicated. Instead, we conclude that a key requirement for Bmper function in the zebrafish is to promote BMP signalling during patterning and morphogenesis of the semicircular canal system

How do genes regulate simple behaviours? Understanding how different neurons in the vertebrate spinal cord are genetically specified

Understanding how the vertebrate central nervous system develops and functions is a major goal of a large body of biological research. This research is driven both by intellectual curiosity about this amazing organ that coordinates our conscious and unconscious bodily processes, perceptions and actions and by the practical desire to develop effective treatments for people with spinal cord injuries or neurological diseases. In recent years, we have learnt an impressive amount about how the nerve cells that communicate with muscles, motoneurons, are made in a developing embryo and this knowledge has enabled researchers to grow motoneurons from stem cells. Building on the success of these studies, researchers have now started to unravel how most of the other nerve cells in the spinal cord are made and function. This review will describe what we currently know about spinal cord nerve cell development, concentrating on the largest category of nerve cells, which are called interneurons. I will then discuss how we can build and expand upon this knowledge base to elucidate the complete genetic programme that determines how different spinal cord nerve cells are made and connected up into neural circuits with particular functions

Specification of CNS glia from neural stem cells in the embryonic neuroepithelium

All the neurons and glial cells of the central nervous system are generated from the neuroepithelial cells in the walls of the embryonic neural tube, the ‘embryonic neural stem cells’. The stem cells seem to be equivalent to the so-called ‘radial glial cells’, which for many years had been regarded as a specialized type of glial cell. These radial cells generate different classes of neurons in a position-dependent manner. They then switch to producing glial cells (oligodendrocytes and astrocytes). It is not known what drives the neuron–glial switch, although downregulation of pro-neural basic helix–loop–helix transcription factors is one important step. This drives the stem cells from a neurogenic towards a gliogenic mode. The stem cells then choose between developing as oligodendrocytes or astrocytes, of which there might be intrinsically different subclasses. This review focuses on the different extracellular signals and intracellular responses that influence glial generation and the choice between oligodendrocyte and astrocyte fates

Brain tumour stem cells: the undercurrents of human brain cancer and their relationship to neural stem cells

Conceptual and technical advances in neural stem cell biology are being applied to the study of human brain tumours. These studies suggest that human brain tumours are organized as a hierarchy and are maintained by a small number of tumour cells that have stem cell properties. Most of the bulk population of human brain tumours comprise cells that have lost the ability to initiate and maintain tumour growth. Although the cell of origin for human brain tumours is uncertain, recent evidence points towards the brain's known proliferative zones. The identification of brain tumour stem cells has important implications for understanding brain tumour biology and these cells may be critical cellular targets for curative therapy