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Elevated Hoxb5b Expands Vagal Neural Crest Pool and Blocks Enteric Neuronal Development in Zebrafish

Howard, Aubrey G. A. and Nguyen, Aaron C. and Tworig, Joshua and Ravisankar, Priya and Singleton, Eileen W. and Li, Can and Kotzur, Grayson and Waxman, Joshua S. and Uribe, Rosa A. (2022) Elevated Hoxb5b Expands Vagal Neural Crest Pool and Blocks Enteric Neuronal Development in Zebrafish. Frontiers in Cell and Developmental Biology, 9 . Art. No. 803370. ISSN 2296-634X. PMCID PMC8841348. doi:10.3389/fcell.2021.803370.

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Neural crest cells (NCCs) are a migratory, transient, and multipotent stem cell population essential to vertebrate embryonic development, contributing to numerous cell lineages in the adult organism. While great strides have been made in elucidating molecular and cellular events that drive NCC specification, comprehensive knowledge of the genetic factors that orchestrate NCC developmental programs is still far from complete. We discovered that elevated Hoxb5b levels promoted an expansion of zebrafish NCCs, which persisted throughout multiple stages of development. Correspondingly, elevated Hoxb5b also specifically expanded expression domains of the vagal NCC markers foxd3 and phox2bb. Increases in NCCs were most apparent after pulsed ectopic Hoxb5b expression at early developmental stages, rather than later during differentiation stages, as determined using a novel transgenic zebrafish line. The increase in vagal NCCs early in development led to supernumerary Phox2b+ enteric neural progenitors, while leaving many other NCC-derived tissues without an overt phenotype. Surprisingly, these NCC-derived enteric progenitors failed to expand properly into sufficient quantities of enterically fated neurons and stalled in the gut tissue. These results suggest that while Hoxb5b participates in vagal NCC development as a driver of progenitor expansion, the supernumerary, ectopically localized NCC fail to initiate expansion programs in timely fashion in the gut. All together, these data point to a model in which Hoxb5b regulates NCCs both in a tissue specific and temporally restricted manner.

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URLURL TypeDescription CentralArticle Paper
Howard, Aubrey G. A.0000-0003-0230-0018
Tworig, Joshua0000-0001-7798-4480
Li, Can0000-0002-9301-7850
Waxman, Joshua S.0000-0002-8132-487X
Uribe, Rosa A.0000-0002-0427-4493
Additional Information:© 2022 Howard, Nguyen, Tworig, Ravisankar, Singleton, Li, Kotzur, Waxman and Uribe. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. Received: 27 October 2021; Accepted: 13 December 2021; Published: 31 January 2022. We offer our sincerest gratitude to Dr. Dan Wagner and to the entire Uribe Lab at Rice University for their insights and support throughout this project. We thank Dr. Budi Utama and the Rice University Shared Equipment Authority on IMARIS image analysis suite, which was indispensable toward this project. We thank Dr. Eric Bridenbaugh and Dr. Mariane Martinez at Olympus for their expert advice on confocal microscopy. We also thank Jonny Diaz and A. Augello Cook for technical assistance. Data Availability Statement: The original contributions presented in the study are included in the article/Supplementary Material, further inquiries can be directed to the corresponding author. Ethics Statement The animal study was reviewed and approved by the Institutional Animal Care and Use Committee (IACUC) of Rice University and Cincinnati Children’s Hospital Medical Center. Author Contributions: AH and RU designed the experiments and wrote the manuscript. RU and AA conceived the idea. AH, AN, JT, PR, ES, CL, GK, and RU performed the experiments. PR and JW created the zebrafish transgenic line. AH and RU performed the data analyses. All the authors contributed to the article and approved the submitted version. Funding: This work was supported by Rice University, a Burroughs Wellcome Fund PDEP Award, Cancer Prevention and Research Institute of Texas (CPRIT) Recruitment of First-Time Tenure Track Faculty Members (No. CPRIT-RR170062) and the NSF CAREER Award (No. 1942019) awarded to RU as well as through the NIH NHLBI (Nos. HL137766, HL141186) awarded to JW. Conflict of Interest: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.
Funding AgencyGrant Number
Rice UniversityUNSPECIFIED
Burroughs Wellcome FundUNSPECIFIED
Cancer Prevention and Research Institute of TexasCPRIT-RR170062
Subject Keywords:neural crest, hox, zebrafish, enteric neuron, differentiation
PubMed Central ID:PMC8841348
Record Number:CaltechAUTHORS:20211103-172542898
Persistent URL:
Official Citation:Howard AGA, Nguyen AC, Tworig J, Ravisankar P, Singleton EW, Li C, Kotzur G, Waxman JS and Uribe RA (2022) Elevated Hoxb5b Expands Vagal Neural Crest Pool and Blocks Enteric Neuronal Development in Zebrafish. Front. Cell Dev. Biol. 9:803370. doi: 10.3389/fcell.2021.803370
Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:111728
Deposited By: Tony Diaz
Deposited On:03 Nov 2021 17:48
Last Modified:02 Mar 2022 22:51

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