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Retinoids produce facial defects in chicken embryos. Outgrowth of the frontonasal mass with accompanying cartilage differentiation and pattern formation is inhibited. In contrast, the development of the mandibular primordia that give rise to the lower beak proceeds normally. To investigate whether the upper beak defect is based on the inhibition of cartilage differentiation specifically in the frontonasal mass, the effects of retinoids on chondrogenesis in micromass (high density) cultures of cells from facial primordia have been studied. When either 10(-6) M retinoic acid or 10(-8) M (E)-4-[2-(5,6,7,8-tetrahydro-5,5,8,8-tetramethyl-2-napthalenyl-1- propenyl]benzoic acid (TTNPB; a stable retinoid) is added to the culture medium, cartilage differentiation is inhibited. Both frontonasal mass and mandible cultures are equally affected. The concentration of TTNPB found in both facial primordia in vivo, after a treatment that produces the defect, is also about 10(-8) M. This rules out preferential accumulation of the retinoid by the frontonasal mass as an explanation for the defect. In fact, the concentration of retinoid found in vivo, should, from the culture studies, be sufficient to markedly inhibit chondrogenesis in both the frontonasal mass and mandibles. The effects of exposure to retinoids in the intact face appear to be different to those in culture. Furthermore, when cells from retinoid-treated facial primordia are cultured in micromass, the extent and pattern of chondrogenesis in frontonasal mass cultures is identical to that of cells from untreated primordia. Cartilage differentiation in mandible cultures is slightly affected. These findings suggest that retinoids do not produce the specific facial defect by directly interfering with cartilage differentiation.

Chondrogenesis of mesenchymal cells from the frontonasal mass, mandibles and maxillae of stage-24 chick embryos has been investigated in micromass (high-density) cultures. Distinct differences in the amount and pattern of cartilage differentiation are found. In cultures of frontonasal mass cells, a central sheet of cartilage develops; in cultures of mandible cells, less cartilage differentiates and nodules form; while in cultures of maxillae cells, virtually no chondrogenesis takes place. The same patterns of cartilage are found in cultures established from stage-20 embryos. At stage 28, frontonasal mass cultures form cartilage nodules and the number of nodules in mandible cultures is markedly decreased. There are striking parallels between the chondrogenic patterns of cells from the face and limb buds in micromass culture. The frontonasal mass cell cultures of stage-20 and -24 chick embryos resemble those established from the progress zone of limb buds. The progress zone is an undifferentiated region of the limb in which positional cues operate. Cultures established from the frontonasal mass of stage-28 chick embryos and from the mandibles of all stages resemble cultures of whole limb buds. These contain a mixture of committed and uncommitted cells. Ectoderm from facial primordia locally inhibits chondrogenesis in micromass cultures and this could provide a positional cue. The differences in chondrogenic potential of cells from facial primordia may underlie the specific retinoid effects on the frontonasal mass.