The DOI matches its Crossref record; 16 of the 16 references it cites were found in a registry or an index.
Specification of positional identity in forebrain organoids
Open accessAbstract
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. Supplying forebrain organoids with a developmental signaling gradient induces topographical patterning along dorso-ventral and antero-posterior axes.
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Metadata
- Authors
- Cederquist, G. Y., Asciolla, J. J., Tchieu, J., Walsh, R. M., Cornacchia, D., Resh, M. D., & Studer, L.
- Venue
- Nature Biotechnology
- Published
- 2019-04
- Volume
- 37
- Issue
- 4
- Pages
- 436-444
- ISSN
- 0733-222X (ISSN-L)
- 1087-0156
- 1546-1696
- OpenAlex
- W2935521291
- Cited by
- 332
- References
- 16
- FWCI
- 12.32
- Type
- journal article
- Language
- en
- Open access
- green
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