Fgf8 dosage determines midfacial integration and polarity within the nasal and optic capsules

Craniofacial development requires an exquisitely timed and positioned cross-talk between the embryonic cephalic epithelia and mesenchyme. This cross-talk underlies the precise translation of patterning processes and information into distinct, appropriate skeletal morphologies. The molecular and cellular dialogue includes communication via secreted signaling molecules, including Fgf8, and effectors of their interpretation. Herein, we use genetic attenuation of Fgf8 in mice and perform gain-of-function mouse-chick chimeric experiments to demonstrate that significant character states of the frontonasal and optic skeletons are dependent on Fgf8. Notably, we show that the normal orientation and polarity of the nasal capsules and their developing primordia are dependent on Fgf8. We further demonstrate that Fgf8 is required for midfacial integration, and provide evidence for a role for Fgf8 in optic capsular development. Taken together, our data highlight Fgf8 signaling in craniofacial development as a plausible target for evolutionary selective pressures.

► We use genetic attenuation to show Fgf8 dosage dependence for cranial morphogenesis.
► Lowered Fgf8 dosage results in apoptotic changes during optic capsular development.
► Normal nasal capsule structural orientation and polarity is Fgf8 dependent.
► Midfacial integration involving the trabecular basal plate is Fgf8 dependent.
► Fgf8 attenuation leads to capsular asymmetries which has evolutionary implications.