Goosecoid acts cell autonomously in mesenchyme-derived tissues during craniofacial development

Mice homozygous for a targeted deletion of the homeobox gene Goosecoid (Gsc ) have multiple craniofacial defects. To understand the mechanisms responsi ble for these defects, the behavior of Gsc-null cells was examined in morul a aggregation chimeras. In these chimeras, Gsc-null cells were marked with beta-galactosidase (beta-gal) activity using the ROSA26 lacZ allele, In add ition, mice with a lacZ gene that had been introduced into the Gsc locus we re used as a guide to visualize the location of Gsc-expressing cells. In Gs c-null <----> wild-type chimeras, tissues that would normally not express G sc were composed of both Gsc-null and wild-type cells that were well mixed, reflecting the overall genotypic composition of the chimeras. However, cra niofacial tissues that would normally express Gsc were essentially devoid o f Gsc-null cells. Furthermore, the nasal capsules and mandibles of the chim eras had defects similar to Gsc-null mice that varied in severity depending upon the proportion of Gsc-null cells. These results combined with the ana lysis of Gsc-null mice suggest that Gsc functions cell autonomously in mese nchyme-derived tissues of the head. A developmental analysis of the tympani c ring bone, a bone that is always absent in Gsc-null mice because of defec ts at the cell condensation stage, showed that Gsc-null cells had the capac ity to form the tympanic ring condensation in the presence of wild-type cel ls. However, analysis of the tympanic ring bones of 18.5 d.p.c, chimeras su ggests that Gsc-null cells were not maintained. The participation of Gsc-nu ll cells in the tympanic ring condensation of chimeras may be an epigenetic phenomenon that results in a local environment in which more precursor cel ls are present. Thus, the skeletal defects observed in Gsc-null mice may re flect a regional reduction of precursor cells during embryonic development.