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Until now, it was unclear as to which genes control differences between the upper and lower jaw of the vertebrate head. Jawed vertebrates evolved from jawless ancest ors over 400 million years ago, and the evolution of a biting lower jaw was a critical step in vertebrate evolution. Comparative studies of vertebrate embryos suggest that lower jaws arose during evolution through changes in patterning along the proximodistal (PD) axis of the jaw as it forms.

The jaw is one of a series of segmental reiterated structures called pharyngeal arches, and its PD axis, like appendages such as limbs, extends from the base of the arch to its tip. How this axis is established is still debated, but like limbs it clearly involves Dlx homeobox transcription factors related to distalless, a key regulator of appendage development in Drosophila.

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