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Lmx1b Modulates Extracellular Matrix Expression During Limb Dorsalization
Author(s) -
Feenstra Jennifer Marie,
Kanaya Kohei,
Pira Charmaine U,
Oberg Kerby C
Publication year - 2009
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.23.1_supplement.470.4
Subject(s) - homeobox , biology , emx2 , limb development , transcription factor , extracellular matrix , in situ hybridization , gene expression , gene , microbiology and biotechnology , limb bud , anatomy , genetics
. Lmx1b is a homeodomain transcription factor that is known to regulate dorsal limb identity and Lmx1b knockout (KO) mice develop nearly symmetrical ventral‐ventral limbs. Currently, downstream limb‐specific targets of Lmx1b are poorly defined. To identify and characterize potential limb‐specific genes targeted by Lmx1b, we compared gene arrays from Lmx1b KO and wild type (WT) mouse limbs harvested during limb outgrowth and patterning, i.e., 11.5, 12.5, and 13.5 days post coitum (dpc). Gene expression was analyzed using replicate Affymetrix 430 2.0 mouse genome arrays. Real‐time PCR confirmed microarray results and whole mount in situ hybridization localized gene expression. Genes that were differentially expressed throughout this period of limb development included 46 significantly up‐regulated and 10 down‐regulated genes. Lmx1b up‐regulated several genes linked to tendon and bone formation including: Emx2 (a homeodomain transcription factor), several extracellular matrix (ECM) proteoglycans ( Kera, Lum, Acan ) and two Matrilins ( Matn1, Matn4 ). Real‐time PCR confirmed differential expression and whole mount in situ hybridization localized expression to the dorsal tendon primordia. These data suggest that Emx2 and a unique collection of ECM‐associated factors orchestrate Lmx1b‐regulated dorsalization by altering the environment in which tendon formation and/or attachment occur. Grant Funding Source NICHD ‐ HD39421