Early interneuron dysfunction in ALS: insights from a mutant sod1 zebrafish model.

Objective: To determine, when, how, and which neurons initiate the onset of pathophysiology in amyotrophic lateral sclerosis (ALS) using a transgenic mutant sod1 zebrafish model and identify neuroprotective drugs.

Methods: Proteinopathies such as ALS involve mutant proteins that misfold and activate the heat shock stress response (HSR). The HSR is indicative of neuronal stress, and we used a fluorescent hsp70-DsRed reporter in our transgenic zebrafish to track neuronal stress and to measure functional changes in neurons and muscle over the course of the disease.

Antibody development and use in chromogenic and fluorescent immunostaining.

Antibody-based detection of protein distribution patterns both in wholemount and on sections revolutionized Xenopus research and ushered in the visual-based era of Xenopus data presentation. The ability to view the distribution of a gene product throughout an embryo makes it possible to rapidly map normal expression profiles and profiles that have been altered by an experimental intervention. The main limiting element in Xenopus immunostaining techniques has always been the availability of antibodies that work well on fixed whole embryos, a problem that persists.

Dynamic modification of the ETS transcription factor PEA3 by sumoylation and p300-mediated acetylation.

Transcription factor activity is often controlled through the dynamic use of post-translational modifications. Two such modifications are acetylation and sumoylation, which both occur on lysine residues, providing the opportunity for cross-talk at the molecular level. Here, we focussed on the ETS-domain transcription factor PEA3 and studied the potential interplay between these two modifications.

Characterisation of a new regulator of BDNF signalling, Sprouty3, involved in axonal morphogenesis in vivo.

During development, many organs, including the kidney, lung and mammary gland, need to branch in a regulated manner to be functional. Multicellular branching involves changes in cell shape, proliferation and migration. Axonal branching, however, is a unicellular process that is mediated by changes in cell shape alone and as such appears very different to multicellular branching.

FoxG1 and TLE2 act cooperatively to regulate ventral telencephalon formation.

FoxG1 is a conserved transcriptional repressor that plays a key role in the specification, proliferation and differentiation of the telencephalon, and is expressed from the earliest stages of telencephalic development through to the adult. How the interaction with co-factors might influence the multiplicity and diversity of FoxG1 function is not known. Here, we show that interaction of FoxG1 with TLE2, a Xenopus tropicalis co-repressor of the Groucho/TLE family, is crucial for regulating the early activity of FoxG1.