Lmx1b expression during joint and tendon formation: localization and evaluation of potential downstream targets.
The tetrapod limb exhibits distinct dorsoventral joint, tendon, and muscle asymmetry. The LIM-homeodomain transcription factor, Lmx1b, is required to achieve the dorsal character of these structures, but the mechanism by which Lmx1b orchestrates this asymmetrical development is unknown. To identify target tissues and genes regulated by Lmx1b, we examined Lmx1b expression during joint, tendon and muscle formation (9.5-16.5 dpc) and the expression of several genes spatially restricted to developing joints and associated tissues in normal and Lmx1b knockout (KO) mice including: Gdf-5, sFrp2, sFrp3, Six1 and Six2. Lmx1b was diffusely expressed in the undifferentiated dorsal mesoderm of the emerging limb bud (E9.5-E11.5). With progressive proximal to distal differentiation, Lmx1b expression localized to dorsal joint-forming regions, to developing tendons and ligaments, but not to migrating myocytes (E13.5-15.5). By E16.5, mature tendon and ligament associations were evident and Lmx1b expression had regressed. The expression patterns of Gdf-5 and sFrp3 at E15.5 were symmetrical along the dorsoventral axis in normal and Lmx1b KO mice. sFrp2, Six1 and Six2 exhibited asymmetrical dorsoventral expression and in Lmx1b KO mice, this asymmetry is lost; however, none were solely restricted to or excluded from dorsal Lmx1b expressing tissues.
Dreyer
Sandra D
SD
Department of Pathology and Human Anatomy, Loma Linda University, 24785 Stewart St., Loma Linda, CA 92350, USA.
Naruse
Takuji
T
Morello
Roy
R
Zabel
Bernhard
B
Winterpacht
Andreas
A
Johnson
Randy L
RL
Lee
Brendan
B
Oberg
Kerby C
KC
D000818:Animals; D005260:Female; D018507:Gene Expression Regulation, Developmental / Q000235:genetics / Q000502:physiology*; D006614:Hindlimb / Q000196:embryology* / Q000378:metabolism; D018398:Homeodomain Proteins / Q000096:biosynthesis* / Q000235:genetics; D007596:Joints / Q000196:embryology* / Q000378:metabolism; D060850:LIM-Homeodomain Proteins; D018878:Limb Buds / Q000196:embryology; D051379:Mice; D018345:Mice, Knockout; D011247:Pregnancy; D013710:Tendons / Q000196:embryology* / Q000378:metabolism; D014157:Transcription Factors
D018398:Homeodomain Proteins; C112149:LIM homeobox transcription factor 1 beta; D060850:LIM-Homeodomain Proteins; D014157:Transcription Factors