title: Detection of genes regulated by Lmx1b during limb dorsalization.
abstract: Lmx1b is a homeodomain transcription factor that regulates dorsal identity during limb development. Lmx1b knockout (KO) mice develop distal ventral-ventral limbs. Although induction of Lmx1b is linked to Wnt7a expression in the dorsal limb ectoderm, the downstream targets of Lmx1b that accomplish limb dorsalization are unknown. To identify genes targeted by Lmx1b, we compared gene arrays from Lmx1b KO and wild type mouse limbs during limb dorsalization, i.e., 11.5, 12.5, and 13.5 days post coitum. We identified 54 target genes that were differentially expressed in all three stages. Several skeletal targets, including Emx2, Matrilin1 and Matrilin4, demonstrated a loss of scapular expression in the Lmx1b KO mice, supporting a role for Lmx1b in scapula development. Furthermore, the relative abundance of extracellular matrix-related soft tissue targets regulated by Lmx1b, such as collagens and proteoglycans, suggests a mechanism that includes changes in the extracellular matrix composition to accomplish limb dorsalization. Our study provides the most comprehensive characterization of genes regulated by Lmx1b during limb development to-date and provides targets for further investigation.
authors.affiliation: Division of Human Anatomy, Department of Pathology and Human Anatomy, Loma Linda University School of Medicine, Loma Linda, CA 92350, USA.
authors.forename: Jennifer M
authors.initials: JM
authors.lastname: Feenstra
authors.forename: Kohei
authors.initials: K
authors.lastname: Kanaya
authors.forename: Charmaine U
authors.initials: CU
authors.lastname: Pira
authors.forename: Sarah E
authors.initials: SE
authors.lastname: Hoffman
authors.forename: Richard J
authors.initials: RJ
authors.lastname: Eppey
authors.forename: Kerby C
authors.initials: KC
authors.lastname: Oberg
mesh_terms: D000818:Animals; D019521:Body Patterning; D064236:Cartilage Oligomeric Matrix Protein; D003238:Connective Tissue / Q000196:embryology; D004622:Embryo, Mammalian / Q000166:cytology / Q000196:embryology; D047108:Embryonic Development; D016326:Extracellular Matrix Proteins / Q000235:genetics / Q000378:metabolism; D005121:Extremities / Q000196:embryology*; D018507:Gene Expression Regulation, Developmental; D006023:Glycoproteins / Q000235:genetics / Q000378:metabolism; D018398:Homeodomain Proteins / Q000235:genetics / Q000378:metabolism; D060850:LIM-Homeodomain Proteins / Q000235:genetics / Q000378:metabolism*; D064235:Matrilin Proteins; D051379:Mice; D018345:Mice, Knockout; D018919:Neovascularization, Physiologic; D009474:Neurons / Q000166:cytology / Q000378:metabolism; D020411:Oligonucleotide Array Sequence Analysis; D012540:Scapula / Q000196:embryology; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D000099260:Empty Spiracles Homeobox Proteins
chemical_list: D064236:Cartilage Oligomeric Matrix Protein; D016326:Extracellular Matrix Proteins; D006023:Glycoproteins; D018398:Homeodomain Proteins; D060850:LIM-Homeodomain Proteins; D064235:Matrilin Proteins; D014157:Transcription Factors; D000099260:Empty Spiracles Homeobox Proteins; C112149:LIM homeobox transcription factor 1 beta; C577540:Matn1 protein, mouse; C577547:Matn4 protein, mouse; C577553:TSP5 protein, human