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Elevated Hoxb5b expands vagal neural crest pool and blocks enteric neuronal development in zebrafish

Provisionally accepted
The final version of the article will be published here soon pending final quality checks
 Aubrey G. Howard IV1,  Aaron C. Nguyen1,  Joshua Tworig2, Priya Ravisankar3, 4, Eileen W. Singleton1, Can Li2, Grayson Kotzur1,  Joshua S. Waxman4 and  Rosa A. Uribe1*
  • 1Rice University, United States
  • 2California Institute of Technology, United States
  • 3Allen Institute for Immunology, United States
  • 4Department of Pediatrics, College of Medicine, University of Cincinnati, United States

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.

Keywords: Neural Crest, hox, Zebrafish, enteric neuron, differentiation

Received: 27 Oct 2021; Accepted: 13 Dec 2021.

Copyright: © 2021 Howard IV, 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.

* Correspondence: Dr. Rosa A. Uribe, Rice University, Houston, 77005, Texas, United States