Coronin 1A depletion restores the nuclear stability and viability of Aip1/Wdr1-deficient neutrophils.

Actin dynamics is central for cells, and especially for the fast-moving leukocytes. The severing of actin filaments is mainly achieved by cofilin, assisted by Aip1/Wdr1 and coronins. We found that in Wdr1-deficient zebrafish embryos, neutrophils display F-actin cytoplasmic aggregates and a complete spatial uncoupling of phospho-myosin from F-actin. They then undergo an unprecedented gradual disorganization of their nucleus followed by eruptive cell death. Their cofilin is mostly unphosphorylated and associated with F-actin, thus likely outcompeting myosin for F-actin binding. Myosin inhibition reproduces in WT embryos the nuclear instability and eruptive death of neutrophils seen in Wdr1-deficient embryos. Strikingly, depletion of the main coronin of leukocytes, coronin 1A, fully restores the cortical location of F-actin, nuclear integrity, viability, and mobility of Wdr1-deficient neutrophils in vivo. Our study points to an essential role of actomyosin contractility in maintaining the integrity of the nucleus of neutrophils and a new twist in the interplay of cofilin, Wdr1, and coronin in regulating F-actin dynamics.

Patterns of cortical reorganization in the adult marmoset after a cervical spinal cord injury.

In the present study, we used microelectrode recordings of multiunit responses to evaluate patterns of the reactivation of somatosensory cortex after sensory loss produced by spinal cord lesions in the common marmoset (Callithrix jacchus). These New World monkeys have become a popular model in studies of cortical organization and function. Primary somatosensory cortex and adjoining somatosensory areas can become extensively deactivated by lesions of somatosensory afferents as they ascend in the dorsal columns of the cervical spinal cord. Six to 7 weeks after complete lesions of the cuneate fasciculus subserving the forelimb at cervical levels 5-6, the hand region in contralateral areas 3b and 1 was reactivated by inputs from the forelimb, but excluded representations of some or all digits. In a similar manner, recording sites from the forelimb region of areas 2-5 responded to parts of the forelimb but not to digits after an extensive lesion of the contralateral cuneate fasciculus at C5-C6. Lesions that damaged only the gracile fasciculus or a small percentage of the cuneate fasciculus did not produce changes in the gross hand representation in contralateral areas 3b, 3a, 1, and 2. Finally, a complete but lower lesion of the cuneate fasciculus at C8 produced some abnormalities in the reactivation, but the digits were represented. The results indicate that areas 3a, 3b, 1, and 2-5 of the somatosensory cortex are extensively reactivated after large, apparently complete lesions of the contralateral cuneate fasciculus, but afferents from the digits may not contribute to their reactivation.

Chondroitinase ABC promotes selective reactivation of somatosensory cortex in squirrel monkeys after a cervical dorsal column lesion.

After large but incomplete lesions of ascending dorsal column afferents in the cervical spinal cord, the hand representation in the contralateral primary somatosensory cortex (area 3b) of monkeys is largely or completely unresponsive to touch on the hand. However, after weeks of spontaneous recovery, considerable reactivation of the hand territory in area 3b can occur. Because the reactivation process likely depends on the sprouting of remaining axons from the hand in the cuneate nucleus of the lower brainstem, we sought to influence cortical reactivation by treating the cuneate nucleus with an enzyme, chondroitinase ABC, that digests perineuronal nets, promoting axon sprouting. Dorsal column lesions were placed at a spinal cord level (C5/C6) that allowed a portion of ascending afferents from digit 1 to survive in squirrel monkeys. After 11-12 wk of recovery, the contralateral forelimb cortex was reactivated by stimulating digit 1 more extensively in treated monkeys than in control monkeys. The results are consistent with the proposal that the treatment enhances the sprouting of digit 1 afferents in the cuneate nucleus and that this sprouting allowed these preserved inputs to activate cortex more effectively.