Rostral growth of commissural axons requires the cell adhesion molecule MDGA2

Background: Long-distance axonal growth relies on the precise interplay of guidance cues and cell adhesion molecules. While guidance cues provide positional and directional information for the advancing growth cone, cell adhesion molecules are essential in enabling axonal advancement. Such a dependence on adhesion as well as guidance molecules can be well observed in dorsal commissural interneurons, which follow a highly stereotypical growth and guidance pattern. The mechanisms and molecules involved in the attraction and outgrowth towards the ventral midline, the axon crossing towards the contralateral side, the rostral turning after midline crossing as well as the guidance along the longitudinal axis have been intensely studied. However, little is known about molecules that provide the basis for commissural axon growth along the anterior-posterior axis. Results: MDGA2, a recently discovered cell adhesion molecule of the IgCAM superfamily, is highly expressed in dorsolaterally located (dI1) spinal interneurons. Functional studies inactivating MDGA2 by RNA interference (RNAi) or function-blocking antibodies demonstrate that either treatment results in a lack of commissural axon growth along the longitudinal axis. Moreover, results from RNAi experiments targeting the contralateral side together with binding studies suggest that homophilic MDGA2 interactions between ipsilaterally projecting axons and post-crossing commissural axons may be the basis of axonal growth along the longitudinal axis. Conclusions: Directed axonal growth of dorsal commissural interneurons requires an elaborate mixture of instructive (guidance) and permissive (outgrowth supporting) molecules. While Wnt and Sonic hedgehog (Shh) signalling pathways have been shown to specify the growth direction of post-crossing commissural axons, our study now provides evidence that homophilic MDGA2 interactions are essential for axonal extension along the longitudinal axis. Interestingly, so far each part of the complex axonal trajectory of commissural axons uses its own set of guidance and growth-promoting molecules, possibly explaining why such a high number of molecules influencing the growth pattern of commissural interneurons has been identified

Black gold: trustworthiness in artistic research (seen from the sidelines of arts and health)

Rigour plays a central role in contemporary research culture. But how appropriate a concept is it to think, perform, and make judgements with on what is trustworthy and excellent in artistic research and its neighbouring field of arts and health? The historical meanings of rigour suggest severity and rigidity: straight lines, austere habits, privations. As a word, rigour has a mixed ancestry – French, Latin, Middle English. Some of its earliest uses coincide with a feudal system of government in Europe, with rigge [verb] meaning to plough a straight line in a narrow strip, and rig [verb] to provide a straight ridge to a house. Rig [noun] a derivation of ridge, was used in England five hundred years ago of human and animal backbones, perhaps reflecting everyday physical burdens. Rigours [noun] conveyed the meting out of un-cautioned punishments and cruelty. While the temperament of rigour might be appropriate for research that follows pre-set norms and standards of repeatability, its use to judge what is trustworthy in artistic research is questionable. Though artistic researchers need to understand the rigour concept, by contrast, artistic research as a kind of ‘thinking through making’ (Ravetz, 2011, 159; Ingold, 2013, 6), places value on improvisation, chance encounter, unforeseen admixture and the in- and outward- folding of process, affect and material. Once it is accepted that poiesis is part of the research process (Ingold, 2013; Haraway, 2016), it becomes apparent that artistic research cannot easily accommodate straight backed rigour

Proper migration and axon outgrowth of zebrafish cranial motoneuron subpopulations require the cell adhesion molecule MDGA2A

The formation of functional neuronal circuits relies on accurate migration and proper axonal outgrowth of neuronal precursors. On the route to their targets migrating cells and growing axons depend on both, directional information from neurotropic cues and adhesive interactions mediated via extracellular matrix molecules or neighbouring cells. The inactivation of guidance cues or the interference with cell adhesion can cause severe defects in neuronal migration and axon guidance. In this study we have analyzed the function of the MAM domain containing glycosylphosphatidylinositol anchor 2A (MDGA2A) protein in zebrafish cranial motoneuron development. MDGA2A is prominently expressed in distinct clusters of cranial motoneurons, especially in the ones of the trigeminal and facial nerves. Analyses of MDGA2A knockdown embryos by light sheet and confocal microscopy revealed impaired migration and aberrant axonal outgrowth of these neurons; suggesting that adhesive interactions mediated by MDGA2A are required for the proper arrangement and outgrowth of cranial motoneuron subtypes