AUTHOR=Dong Zhangji , Chen Xu , Li Yuanyuan , Zhuo Run , Lai Xiaona , Liu Mei 

TITLE=Microtubule Severing Protein Fignl2 Contributes to Endothelial and Neuronal Branching in Zebrafish Development

JOURNAL=Frontiers in Cell and Developmental Biology

VOLUME=8

YEAR=2021

URL=https://www.frontiersin.org/journals/cell-and-developmental-biology/articles/10.3389/fcell.2020.593234

DOI=10.3389/fcell.2020.593234

ISSN=2296-634X

ABSTRACT=<p>Previously, <italic>fidgetin</italic> (<italic>fign</italic>) and its family members <italic>fidgetin-like 1</italic> (<italic>fignl1</italic>) and <italic>fidgetin-like 2</italic> (<italic>fignl2</italic>) were found to be highly expressed during zebrafish brain development, suggesting their functions in the nervous system. In this study, we report the effects of loss-of-function of these genes on development. We designed and identified single-guide RNAs targeted to generate <italic>fign, fignl1</italic>, and <italic>fignl2</italic> mutants and then observed the overall morphological and behavioral changes. Our findings showed that while <italic>fign</italic> and <italic>fignl1</italic> null mutants displayed no significant defects, <italic>fignl2</italic> null zebrafish mutants displayed pericardial edema, reduced heart rate, and smaller eyes; <italic>fignl2</italic> null mutants responded to the light-darkness shift with a lower swimming velocity. <italic>fignl2</italic> mRNAs were identified in vascular endothelial cells by <italic>in situ</italic> hybridization and re-analysis of an online dataset of single-cell RNAseq results. Finally, we used morpholino oligonucleotides to confirm that <italic>fignl2</italic> knockdown resulted in severe heart edema, which was caused by abnormal vascular branching. The zebrafish <italic>fignl2</italic> morphants also showed longer axonal length and more branches of caudal primary neurons. Taken together, we summarize that Fignl2 functions on cellular branches in endothelial cells and neurons. This study reported for the first time that the microtubule-severing protein Fignl2 contributes to cell branching during development.</p>