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Essential function and targets of BMP signaling during midbrain neural crest delamination

Piacentino, Michael L. and Hutchins, Erica J. and Bronner, Marianne E. (2021) Essential function and targets of BMP signaling during midbrain neural crest delamination. Developmental Biology, 477 . pp. 251-261. ISSN 0012-1606. doi:10.1016/j.ydbio.2021.06.003.

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BMP signaling plays iterative roles during vertebrate neural crest development from induction through craniofacial morphogenesis. However, far less is known about the role of BMP activity in cranial neural crest epithelial-to-mesenchymal transition and delamination. By measuring canonical BMP signaling activity as a function of time from specification through early migration of avian midbrain neural crest cells, we found elevated BMP signaling during delamination stages. Moreover, inhibition of canonical BMP activity via a dominant negative mutant Type I BMP receptor showed that BMP signaling is required for neural crest migration from the midbrain, independent from an effect on EMT and delamination. Transcriptome profiling on control compared to BMP-inhibited cranial neural crest cells identified novel BMP targets during neural crest delamination and early migration including targets of the Notch pathway that are upregulated following BMP inhibition. These results suggest potential crosstalk between the BMP and Notch pathways in early migrating cranial neural crest and provide novel insight into mechanisms regulated by BMP signaling during early craniofacial development.

Item Type:Article
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URLURL TypeDescription ItemData/Code
Piacentino, Michael L.0000-0003-1773-031X
Hutchins, Erica J.0000-0002-4316-0333
Bronner, Marianne E.0000-0003-4274-1862
Additional Information:© 2021 Elsevier Inc. Received 31 March 2021, Revised 27 May 2021, Accepted 1 June 2021, Available online 6 June 2021. We would like to thank Megan Martik and Shashank Gandhi for valuable discussion on experiment design and analysis, and Gabriel da Silva Pescador for technical support. We thank Elisa Martí for sharing reagents, Patrick Cannon 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. Funding for this work comes from the National Institutes of Health grants K99DE029240 to M.L.P., K99DE028592 to E.J.H, R01DE027538 and R01DE027568 to M.E.B. Author contributions: Conceptualization: M.L.P., E.J.H., and M.E.B.; Experiment design: M.L.P. and E.J.H.; Experimentation: M.L.P. and E.J.H.; Data analysis: M.L.P.; Data interpretation: M.L.P., E.J.H., and M.E.B.; Manuscript preparation: M.L.P.; Manuscript editing: M.E.B. and E.J.H. Data and code availability: All source data and associated code used for analysis are publicly available on GitHub at Raw RNA-seq results are available in the following NCBI BioProjects: Control replicates BioProject #PRJNA673315 (performed in collaboration with (Hutchins et al., 2021)), and dnBMPR1A-FLAG replicates BioProject #PRJNA717985. The authors declare no competing interests.
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Subject Keywords:Neural crest; Epithelial-to-mesenchymal transition; BMP signaling; RNA Seq; Delamination; Migration
Record Number:CaltechAUTHORS:20210629-192923094
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Official Citation:Michael L. Piacentino, Erica J. Hutchins, Marianne E. Bronner, Essential function and targets of BMP signaling during midbrain neural crest delamination, Developmental Biology, Volume 477, 2021, Pages 251-261, ISSN 0012-1606, (
Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:109649
Deposited By: Tony Diaz
Deposited On:29 Jun 2021 22:37
Last Modified:29 Jun 2021 22:37

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