title: The nuclear orphan receptor COUP-TFII is required for limb and skeletal muscle development.
abstract: The nuclear orphan receptor COUP-TFII is widely expressed in multiple tissues and organs throughout embryonic development, suggesting that COUP-TFII is involved in multiple aspects of embryogenesis. Because of the early embryonic lethality of COUP-TFII knockout mice, the role of COUP-TFII during limb development has not been determined. COUP-TFII is expressed in lateral plate mesoderm of the early embryo prior to limb bud formation. In addition, COUP-TFII is also expressed in the somites and skeletal muscle precursors of the limbs. Therefore, in order to study the potential role of COUP-TFII in limb and skeletal muscle development, we bypassed the early embryonic lethality of the COUP-TFII mutant by using two methods. First, embryonic chimera analysis has revealed an obligatory role for COUP-TFII in limb bud outgrowth since mutant cells are unable to contribute to the distally growing limb mesenchyme. Second, we used a conditional-knockout approach to ablate COUP-TFII specifically in the limbs. Loss of COUP-TFII in the limbs leads to hypoplastic skeletal muscle development, as well as shorter limbs. Taken together, our results demonstrate that COUP-TFII plays an early role in limb bud outgrowth but not limb bud initiation. Also, COUP-TFII is required for appropriate development of the skeletal musculature of developing limbs.
authors.affiliation: Department of Molecular and Cellular Biology, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030, USA.
authors.forename: Christopher T
authors.initials: CT
authors.lastname: Lee
authors.forename: Luoping
authors.initials: L
authors.lastname: Li
authors.forename: Norio
authors.initials: N
authors.lastname: Takamoto
authors.forename: James F
authors.initials: JF
authors.lastname: Martin
authors.forename: Francesco J
authors.initials: FJ
authors.lastname: Demayo
authors.forename: Ming-Jer
authors.initials: MJ
authors.lastname: Tsai
authors.forename: Sophia Y
authors.initials: SY
authors.lastname: Tsai
mesh_terms: D000818:Animals; D001755:Blastocyst / Q000166:cytology; D051837:COUP Transcription Factor II; D051836:COUP Transcription Factors; D002455:Cell Division; D002465:Cell Movement; D002478:Cells, Cultured; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D047108:Embryonic Development; D005121:Extremities / Q000196:embryology*; D005260:Female; D006720:Homozygote; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D008648:Mesoderm / Q000166:cytology / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D024510:Muscle Development; D018482:Muscle, Skeletal / Q000196:embryology*; D009154:Mutation; D011247:Pregnancy; D011987:Receptors, Steroid / Q000235:genetics / Q000378:metabolism*; D013234:Stem Cells / Q000166:cytology; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*
chemical_list: D051837:COUP Transcription Factor II; D051836:COUP Transcription Factors; D004268:DNA-Binding Proteins; C497587:Nr2f2 protein, mouse; D011987:Receptors, Steroid; D014157:Transcription Factors