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Published May 2023 | Accepted
Journal Article Open

Reprogramming of trunk neural crest to a cranial crest-like identity alters their transcriptome and developmental potential

Abstract

Neural crest cells along the body axis of avian embryos differ in their developmental potential, such that the cranial neural crest forms cartilage and bone whereas the trunk neural crest is unable to do so. Previous studies have identified a cranial crest-specific subcircuit that can imbue the trunk neural crest with the ability to form cartilage after grafting to the head. Here, we examine transcriptional and cell fate changes that accompany this reprogramming. First, we examined whether reprogrammed trunk neural crest maintain the ability to form cartilage in their endogenous environment in the absence of cues from the head. The results show that some reprogrammed cells contribute to normal trunk neural crest derivatives, whereas others migrate ectopically to the forming vertebrae and express cartilage markers, thus mimicking heterotypically transplanted cranial crest cells. We find that reprogrammed trunk neural crest upregulated more than 3000 genes in common with cranial neural crest, including numerous transcriptional regulators. In contrast, many trunk neural crest genes are downregulated. Together, our findings show that reprogramming trunk neural crest with cranial crest subcircuit genes alters their gene regulatory program and developmental potential to be more cranial crest-like.

Additional Information

© 2023 International Society of Differentiation. Published by Elsevier. This work was supported by National Institutes of Health, National Institute of Dental and Craniofacial Research grants 5R01DE027538-05 and 5R01DE024157-07 to M.E.B. S.S.M is supported by a Helen Hay Whitney Foundation postdoctoral fellowship. We would like to thank Jamie Tijerina and Rochelle Diamond at the Caltech Flow Cytometry Cell Sorting Facility for cell sorting, Igor Antoshechkin of the Caltech Millard and Muriel Jacobs Genetics and Genomics Laboratory for library sequencing, and the Beckman Institute Biological Imaging Facility for microscopy support. We thank Dr. Michael Piacentino and Dr. Megan Martik for help with RNA-seq data analysis and Dr. Meyer Barembaum and Dr. Shashank Gandhi for the expression constructs used in the electroporation experiments. Data availability. All sequencing data is available on NCBI (BioProject ID PRJNA903529).

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Created:
May 1, 2024
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May 1, 2024