Role for Kinesin KIFC in Nuclear Migration
Hemalatha Muralidharan, Shrobona Guha, Kiran Madugula, Ankita Patil, Sarah A. Bennison, et al.
(see pages 2149–2165)
The first cells of the developing nervous system are radial glial cells, the progenitors of neurons and astrocytes. These elongated cells contact both the ventricular (apical) and pial (basal) surfaces of the neural tube, and, in a process termed interkinetic nuclear migration, their nuclei move first basally then apically during each cell cycle. Mitosis occurs only when the nucleus is at the ventricular surface, whereas DNA replication occurs when the nucleus is at the basal side of the ventricular zone. Interkinetic nuclear migration is mediated by microtubule motor proteins, primarily Kif1a, which moves the nucleus in the basal direction, and dynein, which carries the nucleus apically. Dynein, with assistance from myosin II, also moves the nucleus along microtubules toward the leading process of migrating newborn neurons (Dantas et al., 2016, Cytoskeleton 73:566). Several other motor proteins have minor roles in nuclear translocation. Muralidharan et al. add the kinesin KIFC1 to this list, showing that it helps keep nuclei and neurons headed in the right direction during both interkinetic nuclear migration and neuronal migration.
Knocking down KIFC1 in utero slowed apical nuclear migration in radial glial cells without affecting basal migration. Consequently, at embryonic day 15, fewer KIFC-depleted cells were undergoing mitosis, and more had exited the cell cycle, compared with control cells. Although these effects increased the number of newborn neurons in the intermediate zone, KIFC-depleted neurons did not reach the cortical plate earlier than controls. This failure arose because KIFC-depleted neurons often changed direction while migrating rather than moving consistently toward the cortical plate. In addition, KIFC-depleted neurons migrated more slowly and stopped more often than control neurons. Rescue experiments suggested that the ability of KIFC to cross-link microtubules was essential for normal migration. Finally, in vitro experiments revealed that KIFC prevented sliding of microtubules and helped to maintain the integrity of the nuclear envelope during migration. Based on these results, the authors suggest that cross-linking of microtubules by KIFC is required during both interkinetic nuclear migration and neuron migration to enable dynein to propel the nucleus forward without distorting the nuclear envelope, and to prevent the sliding of microtubules that would cause migration to veer off from a straight path.
Cortical areas showing significant phase coupling with the gastric rhythm, with effect sizes ranging from 0.3 (orange) to 0.5 (yellow). Other colors indicate regions involved in seven previously described resting-state networks. See Rebollo and Tallon-Baudry for details.
Cortical Areas with Activity Coupled to the Stomach Rhythm
Ignacio Rebollo and Catherine Tallon-Baudry
(see pages 2205–2220)
Brain activity is constantly modulated by rhythmic input from peripheral organs, which can affect the processing of sensory information from the environment. For example, the ability to detect faint sensory stimuli varies across both the respiratory and the cardiac cycles (Grund et al., 2022, J Neurosci 42:643). Rebollo and colleagues recently discovered that the gastric rhythm—an electrical rhythm constantly generated by cells in the stomach wall regardless of stomach contents—is coupled to resting-state activity in several brain areas. Rebollo and Tallon-Baudry now provide more detail about which brain areas are involved in this gastric network.
The authors used electrogastrography to measure the gastric rhythm and used functional MRI to measure brain activity while participants were resting and not actively digesting a meal. They then computed a phase-locking value to identify brain voxels whose blood oxygen level-dependent signals fluctuated with the gastric rhythm, regardless of the amplitude or phase difference between the two rhythms. Not surprisingly, some of the brain regions most strongly coupled to the gastric rhythm were somatosensory areas known to process visceral information and motor areas that regulate sympathetic input to the gut. Premotor areas involved in integrating sensory information to guide behavior were also coupled to the gastric rhythm. More surprisingly, activity in primary auditory and visual cortical areas, as well as some areas involved in the theory of mind and language processing were strongly coupled to the gastric rhythm. In contrast, relatively few areas that were coupled to the gastric rhythm were components of previously described saliency, control, and default resting-state networks.
These results confirm and extend previous work showing that the gastric rhythm is strongly coupled to activity in most primary sensory areas in the cortex. The pathways mediating this coupling and the direction of the influence remain unclear. One possibility is that the gastric rhythm influences activity in primary somatosensory cortex via direct visceral input, and the somatosensory cortex then spreads this influence to other primary sensory areas through corticocortical connections. Future work should investigate this possibility and examine the extent to which the gastric rhythm influences auditory and visual processing.
Footnotes
This Week in The Journal was written by Teresa Esch, Ph.D.
