Paxillin is crucial for thymus and parathyroid development by regulating the architecture of the third pharyngeal pouch endoderm.

The paxillin (PXN) protein is a key component of focal adhesions in which it primarily functions as a molecular scaffold to spatiotemporally integrate diverse signalling networks to transduce intracellular responses. In this study, using loss-of-function genetics in mice, we investigated whether the Pxn gene has a role in the morphogenesis of the pharyngeal apparatus and whether it interacts with the Tbx1 gene, which encodes a key transcription factor required in pharyngeal development. Conditional deletion of Pxn in the Tbx1 expression domain did not cause cardiac defects. Instead, the germline Pxn mutation led to cardiac anomalies and to morphogenetic defects of the third pharyngeal pouch (3PP). We found that in Pxn deleted embryos, the 3PP was hypoplastic, lacked the expression of Gcm2, a gene that marks the parathyroid domain, but expressed FoxN1, a gene marking the thymic domain. Consistently, the parathyroids did not develop, and the thymus was hypoplastic and/or malpositioned. The reduced dosage of Tbx1 had a more severe effect on cardio-pharyngeal defects of Pxn−/− embryos, suggesting an interaction between Pxn and Tbx1. Thus, a novel function of Pxn in the control of parathyroid and thymic development has been discovered, probably through a function in the pouch endoderm, and intriguingly we found a strong genetic interaction between Tbx1 and Pxn.