AUTHOR=Jia Shihai , Oliver Jeremie D. , Turner Emma C. , Renouard Maranda , Bei Marianna , Wright J. T. , D’Souza Rena N. 

TITLE=Pax9’s Interaction With the Ectodysplasin Signaling Pathway During the Patterning of Dentition

JOURNAL=Frontiers in Physiology

VOLUME=11

YEAR=2020

URL=https://www.frontiersin.org/journals/physiology/articles/10.3389/fphys.2020.581843

DOI=10.3389/fphys.2020.581843

ISSN=1664-042X

ABSTRACT=<p>In these studies, we explored for the first time the molecular relationship between the paired-domain-containing transcription factor, <italic>Pax9</italic>, and the ectodysplasin (<italic>Eda</italic>) signaling pathway during mouse incisor formation. Mice that were deficient in both <italic>Pax9</italic> and <italic>Eda</italic> were generated, and the status of dentition analyzed in all progeny using gross evaluation and histomorphometric means. When compared to wildtype controls, <italic>Pax9<sup>+/–</sup>Eda<sup>–/–</sup></italic> mice lack mandibular incisors. Interestingly, <italic>Fgf</italic> and <italic>Shh</italic> signaling are down-regulated while <italic>Bmp4</italic> and <italic>Lef1</italic> appear unaffected. These findings suggest that <italic>Pax9</italic>-dependent signaling involves the <italic>Eda</italic> pathway and that this genetic relationship is important for mandibular incisor development. Studies of records of humans affected by mutations in <italic>PAX9</italic> lead to the congenital absence of posterior dentition but interestingly involve agenesis of mandibular central incisors. The latter phenotype is exhibited by individuals with <italic>EDA</italic> or <italic>EDAR</italic> mutations. Thus, it is likely that <italic>PAX9</italic>, in addition to playing a role in the formation of more complex dentition, is also involved with <italic>EDA</italic> signaling in the initiation of odontogenesis within the incisal domain.</p>