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ABSTRACT The considerably slow pace of human brain development correlates with an evolutionary increase in brain size, cell numbers, and expansion of neuronal structures, with axon tracts undergoing an even greater evolutionary increase than other neuronal domains. However, whether tempo is responsible for these differences in magnitude, and how, remains to be determined. Here, we used brain organoids to investigate this and observed that human axon tracts spend more time growing and extend farther compared to those of mice, independent of their tissue environment. Single cell RNA sequencing analysis pointed to a subset of calcium-permeable ion channels expressed throughout neuron development, including during axon tract outgrowth. Calcium imaging during early neuron development consistently revealed a reduced calcium influx in human neurons compared to mouse neurons. Stimulating calcium influx and increasing cAMP levels resulted in premature halting of axon tract outgrowth and shorter axon tracts, mimicking the mouse phenotype, while abrogating calcium influx led to an even longer phase of axon tract outgrowth and longer axon tracts in humans. Thus, evolutionary differences in calcium regulation set the tempo of neuronal development, by extending the time window to foster the more elaborated human neuron morphology.
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Computational simulations reveal that Abl activity controls cohesiveness of actin networks in growth cones
How do single-molecule dynamics produce multimicron-scale changes in actin organization in an extending axon? Comparison of computational simulations to in vivo data suggests that Abl kinase and Arp2/3 expand actomyosin networks by fragmenting them into multiple domains, thus toggling the axon between states of local versus global internal connectivity.
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- Award ID(s):
- 2102684
- PAR ID:
- 10609237
- Editor(s):
- Mogilner, Alex
- Publisher / Repository:
- American Society for Cell Biology
- Date Published:
- Journal Name:
- Molecular Biology of the Cell
- Volume:
- 33
- Issue:
- 11
- ISSN:
- 1059-1524
- Format(s):
- Medium: X
- Sponsoring Org:
- National Science Foundation
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- Free Publicly Accessible Full Text
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Accepted Manuscript1.0
- Journal Article:
- https://doi.org/10.1091/mbc.E21-11-0535
