Essential Role of Nr2f Nuclear Receptors in Patterning the Vertebrate Upper Jaw

Publication date: 5 February 2018
Source:Developmental Cell, Volume 44, Issue 3
Author(s): Lindsey Barske, Pauline Rataud, Kasra Behizad, Lisa Del Rio, Samuel G. Cox, J. Gage Crump
The jaw is central to the extensive variety of feeding and predatory behaviors across vertebrates. The bones of the lower but not upper jaw form around an early-developing cartilage template. Whereas Endothelin1 patterns the lower jaw, the factors that specify upper-jaw morphology remain elusive. Here, we identify Nuclear Receptor 2f genes (Nr2fs) as enriched in and required for upper-jaw formation in zebrafish. Combinatorial loss of Nr2fs transforms maxillary components of the upper jaw into lower-jaw-like structures. Conversely, nr2f5 misexpression disrupts lower-jaw development. Genome-wide analyses reveal that Nr2fs repress mandibular gene expression and early chondrogenesis in maxillary precursors. Rescue of lower-jaw defects in endothelin1 mutants by reducing Nr2f dosage further demonstrates that Nr2f expression must be suppressed for normal lower-jaw development. We propose that Nr2fs shape the upper jaw by protecting maxillary progenitors from early chondrogenesis, thus preserving cells for later osteogenesis.

Graphical abstract

Teaser

Barske et al. use combinatorial genetics in zebrafish to identify the Nr2f nuclear receptors as critical factors for specifying upper-jaw identity. Nr2fs selectively repress early cartilage formation in upper-jaw skeletal progenitors, thus creating morphological asymmetry with the lower but not upper jaw forming around a prominent cartilage template.


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