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

Frontiers in Cell and Developmental Biology

Cell and Developmental Biology

Rosa A. Uribe¹  Grayson Kotzur¹  Eileen W. Singleton¹  Aaron C. Nguyen¹  Aubrey G. A. Howard¹  Can Li²  Joshua Tworig²  Joshua S. Waxman³  Priya Ravisankar⁴ 

[1] BioSciences Department, Rice University, Houston, TX, United States;Division of Biology and Biological Engineering, California Institute of Technology, Pasadena, CA, United States;Molecular Cardiovascular Biology Division, Cincinnati Children’s Hospital Medical Center and Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, OH, United States;Molecular Cardiovascular Biology Division, Cincinnati Children’s Hospital Medical Center and Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, OH, United States;Allen Institute of Immunology, Seattle, WA, United States;

关键词: neural crest;    hox;    zebrafish;    enteric neuron;    differentiation;   

DOI  :  10.3389/fcell.2021.803370

 received in 2021-10-27, accepted in 2021-12-13,  发布年份 2022

来源: Frontiers

【 摘 要 】

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.

【 授权许可】

Unknown   
Copyright © 2022 Howard, Nguyen, Tworig, Ravisankar, Singleton, Li, Kotzur, Waxman and Uribe.