title: Goosecoid acts cell autonomously in mesenchyme-derived tissues during craniofacial development.
abstract: Mice homozygous for a targeted deletion of the homeobox gene Goosecoid (Gsc) have multiple craniofacial defects. To understand the mechanisms responsible for these defects, the behavior of Gsc-null cells was examined in morula aggregation chimeras. In these chimeras, Gsc-null cells were marked with beta-galactosidase (beta-gal) activity using the ROSA26 lacZ allele. In addition, mice with a lacZ gene that had been introduced into the Gsc locus were used as a guide to visualize the location of Gsc-expressing cells. In Gsc-null<->wild-type chimeras, tissues that would normally not express Gsc were composed of both Gsc-null and wild-type cells that were well mixed, reflecting the overall genotypic composition of the chimeras. However, craniofacial tissues that would normally express Gsc were essentially devoid of Gsc-null cells. Furthermore, the nasal capsules and mandibles of the chimeras had defects similar to Gsc-null mice that varied in severity depending upon the proportion of Gsc-null cells. These results combined with the analysis of Gsc-null mice suggest that Gsc functions cell autonomously in mesenchyme-derived tissues of the head. A developmental analysis of the tympanic ring bone, a bone that is always absent in Gsc-null mice because of defects at the cell condensation stage, showed that Gsc-null cells had the capacity to form the tympanic ring condensation in the presence of wild-type cells. However, analysis of the tympanic ring bones of 18.5 d.p.c. chimeras suggests that Gsc-null cells were not maintained. The participation of Gsc-null cells in the tympanic ring condensation of chimeras may be an epigenetic phenomenon that results in a local environment in which more precursor cells are present. Thus, the skeletal defects observed in Gsc-null mice may reflect a regional reduction of precursor cells during embryonic development.
authors.affiliation: Department of Molecular Genetics, The University of Texas M.D. Anderson Cancer Center, Houston, TX 77030, USA.
authors.forename: J A
authors.initials: JA
authors.lastname: Rivera-Pérez
authors.forename: M
authors.initials: M
authors.lastname: Wakamiya
authors.forename: R R
authors.initials: RR
authors.lastname: Behringer
mesh_terms: D000818:Animals; D002678:Chimera / Q000235:genetics; D019465:Craniofacial Abnormalities / Q000196:embryology / Q000235:genetics; D004432:Ear, Middle / Q000002:abnormalities / Q000196:embryology; D005147:Facial Bones / Q000196:embryology*; D018507:Gene Expression Regulation, Developmental; D005801:Genes, Homeobox; D051956:Goosecoid Protein; D018398:Homeodomain Proteins / Q000235:genetics*; D008334:Mandible / Q000002:abnormalities / Q000196:embryology; D008648:Mesoderm / Q000166:cytology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009295:Nasal Bone / Q000002:abnormalities / Q000196:embryology; D012097:Repressor Proteins; D012886:Skull / Q000196:embryology*; D014157:Transcription Factors; D001616:beta-Galactosidase / Q000235:genetics
chemical_list: D051956:Goosecoid Protein; C497993:Gsc protein, mouse; D018398:Homeodomain Proteins; D012097:Repressor Proteins; D014157:Transcription Factors; D001616:beta-Galactosidase