Parisi, I. | Search bioRxiv

bioRxiv2020

The ontogeny of multisensory peripersonal space in human infancy: From visual-tactile links to conscious expectations.

The influence of visual object motion on the processing of bodily events offers a marker for the development of human infants perception of themselves in peripersonal space. We presented 4- (n = 20) and 8-month-old (n = 20) infants with an unattended visual object moving towards or away from their body followed by a vibrotactile stimulus on their hands. The 4-month-olds somatosensory evoked potentials (SEPs) were modulated by approaching visual motion, demonstrating the early ontogeny of the cortical multisensory foundations of peripersonal space representations. We also observed rapid changes in these markers within the 8-month-old age group: as infants approach 9 months, salient SEP components were increasingly enhanced by (unexpected) tactile stimuli following receding visual motion. These findings provide important clues to the ontogeny of human self-awareness in the first year of life, and suggest important postnatal developments in infants expectations about interactions between the body and the external world.

neuroscience↗

bioRxiv2020

The ciliary protein IFT88 controls post-natal cartilage thickness and influences development of osteoarthritis.

Mechanical and biological cues drive cellular signalling in cartilage development, health, and disease. Proteins of the primary cilium, implicated in transduction of biophysiochemical signals, control cartilage formation during skeletal development, but their influence in post-natal cartilage remains unknown. Ift88fl/fl and AggrecanCreERT2 mice were crossed to create a cartilage-specific, inducible knockout mouse AggrecanCreERT2;Ift88fl/fl. Tibial articular cartilage (AC) thickness was assessed, through adolescence and adulthood, by histomorphometry and integrity by OARSI score. In situ mechanisms were investigated by immunohistochemistry (IHC), RNA scope and qPCR of micro-dissected cartilage. OA was induced by surgical destabilisation (DMM). Mice voluntarily exercised using wheels. Deletion of IFT88 resulted in progressive reductions in medial AC thickness during adolescence, and marked atrophy in adulthood. At 34 weeks of age, medial thickness was reduced from 104.00m, [100.30-110.50, 95% CI] in Ift88fl/fl to 89.42m [84.00-93.49, 95% CI] in AggrecanCreERT2;Ift88fl/fl (p<0.0001), associated with reductions in calcified cartilage. Occasionally, atrophy was associated with complete, spontaneous, medial cartilage degradation. Following DMM, AggrecanCreERT2;Ift88fl/fl mice had increased OA scores. Atrophy in mature AC was not associated with obvious increases in aggrecanase-mediated destruction or chondrocyte hypertrophy. Ift88 expression positively correlated with Tcf7l2, connective tissue growth factor (Ctgf) and Enpp1. RNA scope revealed increased hedgehog (Hh) signalling (Gli1), associated with reductions in Ift88, in AggrecanCreERT2;Ift88fl/fl cartilage. Wheel exercise restored both AC thickness and levels of Hh signalling in AggrecanCreERT2;Ift88fl/fl. Our results demonstrate that IFT88 is chondroprotective, regulating AC thickness, potentially by thresholding a Hh response to physiological loading that controls cartilage calcification.

molecular biology↗