title: Retinoic acid controls expression of tissue remodeling genes Hmgn1 and Fgf18 at the digit-interdigit junction.
abstract: Previous studies on retinoic acid receptor (RAR) mutants suggested that retinoic acid (RA) is required for loss of interdigital mesenchyme during digit formation. Here, we report that the RA-generating enzyme retinaldehyde dehydrogenase-2 (Raldh2) is expressed in the interdigital mesenchyme whereas Cyp26b1, controlling RA degradation, is expressed in digits, limiting autopodal RA action to the interdigital zones. Embryonic day 13.5 Raldh2-/- mouse embryos lose expression of the RARE-lacZ RA-reporter transgene and matrix metalloproteinase-11 (Mmp11) throughout the interdigital mesenchyme, while expression of RARb, Fgf18, and high mobility group N1 (Hmgn1) is lost at the digit-interdigit junction. Raldh2-/- autopods exhibit reduced interdigital apoptosis associated with loss of Bmp7 expression, but Bmp2, Bmp4, Msx2, and Fgf8 were unaffected. Although interdigital expression of Hmgn1 was greatly down-regulated in Raldh2-/- autopods, complementary expression of Sox9 in digit cartilage was unaffected. Regulation of Hmgn1 and Fgf18 at the digit-interdigit junction suggests RA controls tissue remodeling as well as apoptosis.
authors.affiliation: Burnham Institute for Medical Research, Development and Aging Program, La Jolla, California, USA.
authors.forename: Xianling
authors.initials: X
authors.lastname: Zhao
authors.forename: Thomas
authors.initials: T
authors.lastname: Brade
authors.forename: Thomas J
authors.initials: TJ
authors.lastname: Cunningham
authors.forename: Gregg
authors.initials: G
authors.lastname: Duester
mesh_terms: D000445:Aldehyde Oxidoreductases / Q000378:metabolism*; D000818:Animals; D017209:Apoptosis; D019485:Bone Morphogenetic Proteins / Q000378:metabolism; D047108:Embryonic Development; D005346:Fibroblast Growth Factors / Q000378:metabolism*; D024241:HMGN1 Protein / Q000378:metabolism*; D006614:Hindlimb / Q000196:embryology / Q000378:metabolism; D053507:Matrix Metalloproteinase 11 / Q000378:metabolism; D051379:Mice; D009154:Mutation; D018168:Receptors, Retinoic Acid / Q000378:metabolism; D055758:SOX9 Transcription Factor / Q000378:metabolism; D015398:Signal Transduction; D014212:Tretinoin / Q000378:metabolism*
chemical_list: D019485:Bone Morphogenetic Proteins; D024241:HMGN1 Protein; D018168:Receptors, Retinoic Acid; D055758:SOX9 Transcription Factor; C527933:Sox9 protein, mouse; C113569:fibroblast growth factor 18; C082925:retinoic acid receptor beta; D014212:Tretinoin; D005346:Fibroblast Growth Factors; D000445:Aldehyde Oxidoreductases; C470579:RALDH2 protein, mouse; D053507:Matrix Metalloproteinase 11