Specification of positional identity in forebrain organoids Research Letter
| Authors: | Cederquist, G. Y.; Asciolla, J. J.; Tchieu, J.; Walsh, R. M.; Cornacchia, D.; Resh, M. D.; Studer, L. |
| Title: | Specification of positional identity in forebrain organoids |
| Abstract: | Human brain organoids generated with current technologies recapitulate histological features of the human brain, but they lack a reproducible topographic organization. During development, spatial topography is determined by gradients of signaling molecules released from discrete signaling centers. We hypothesized that introduction of a signaling center into forebrain organoids would specify the positional identity of neural tissue in a distance-dependent manner. Here, we present a system to trigger a Sonic Hedgehog (SHH) protein gradient in developing forebrain organoids that enables ordered self-organization along dorso-ventral and antero-posterior positional axes. SHH-patterned forebrain organoids establish major forebrain subdivisions that are positioned with in vivo-like topography. Consistent with its behavior in vivo, SHH exhibits long-range signaling activity in organoids. Finally, we use SHH-patterned cerebral organoids as a tool to study the role of cholesterol metabolism in SHH signaling. Together, this work identifies inductive signaling as an effective organizing strategy to recapitulate in vivo-like topography in human brain organoids. © 2019, The Author(s), under exclusive licence to Springer Nature America, Inc. |
| Keywords: | signal transduction; controlled study; human cell; letter; mouse; animal; cytology; metabolism; animals; mice; biological model; signaling; sonic hedgehog protein; hedgehog proteins; neural stem cell; cell differentiation; biotechnology; growth, development and aging; brain; cholesterol; pluripotent stem cell; pluripotent stem cells; neural stem cells; forebrain; prosencephalon; nervous system development; neurogenesis; body patterning; anterior posterior axis; models, neurological; topography; dorsal-ventral patterning; shh protein, human; cholesterol metabolism; humans; human; priority journal; organoids; histological features; organoid; current technology; self organizations; signaling activity; signaling molecules; sonic hedgehogs; spatial topographies; cerebral organoid |
| Journal Title: | Nature Biotechnology |
| Volume: | 37 |
| Issue: | 4 |
| ISSN: | 1087-0156 |
| Publisher: | Nature Publishing Group |
| Date Published: | 2019-04-01 |
| Start Page: | 436 |
| End Page: | 444 |
| Language: | English |
| DOI: | 10.1038/s41587-019-0085-3 |
| PUBMED: | 30936566 |
| PROVIDER: | scopus |
| PMCID: | PMC6447454 |
| DOI/URL: | |
| Notes: | Letter -- Export Date: 1 November 2019 -- Source: Scopus |
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