AUTHOR=Stenzel Amanda , Mumme-Monheit Abigail , Sucharov Juliana , Walker Macie , Mitchell Jennyfer M. , Appel Bruce , Nichols James T. 

TITLE=Distinct and redundant roles for zebrafish her genes during mineralization and craniofacial patterning

JOURNAL=Frontiers in Endocrinology

VOLUME=13

YEAR=2022

URL=https://www.frontiersin.org/journals/endocrinology/articles/10.3389/fendo.2022.1033843

DOI=10.3389/fendo.2022.1033843

ISSN=1664-2392

ABSTRACT=<p>The Notch pathway is a cell-cell communication system which is critical for many developmental processes, including craniofacial development. Notch receptor activation induces expression of several well-known canonical targets including those encoded by the <italic>hes</italic> and <italic>her</italic> genes in mammals and zebrafish, respectively. The function of these genes, individually and in combination, during craniofacial development is not well understood. Here, we used zebrafish genetics to investigate <italic>her9</italic> and <italic>her6</italic> gene function during craniofacial development. We found that <italic>her9</italic> is required for osteoblasts to efficiently mineralize bone, while cartilage is largely unaffected. Strikingly, gene expression studies in <italic>her9</italic> mutants indicate that although progenitor cells differentiate into osteoblasts at the appropriate time and place, they fail to efficiently lay down mineralized matrix. This mineralization role of <italic>her9</italic> is likely independent of Notch activation. In contrast, <italic>her9</italic> also functions redundantly with <italic>her6</italic> downstream of Jagged1b-induced Notch activation during dorsoventral craniofacial patterning. These studies disentangle distinct and redundant <italic>her</italic> gene functions during craniofacial development, including an unexpected, Notch independent, requirement during bone mineralization.</p>