Studies on the role of Dlx5 in regulation of chondrocyte differentiation during endochondral ossification in the developing mouse limb.
The homeodomain transcription factor Dlx5 has been implicated in the regulation of chondrocyte and osteoblast differentiation during endochondral ossification in the developing limb. In a gain-of-function approach to directly investigate the role of Dlx5 in chondrocyte maturation, we have used cartilage-specific Col2a1-Dlx5 promoter/enhancer constructs to target overexpression of Dlx5 to the differentiating cartilage models of the limbs of transgenic mice. Targeted overexpression of Dlx5 in cartilage rudiments results in the formation of shortened skeletal elements containing excessive numbers of hypertrophic chondrocytes and expanded domains of expression of Ihh and type X collagen, molecular markers of hypertrophic maturation. This suggests that hypertrophic differentiation is enhanced in response to Dlx5 misexpression. Skeletal elements overexpressing Dlx5 also exhibit a marked reduction in the zone of proliferation, indicating that overexpression of Dlx5 reduces chondrocyte proliferation concomitant with promoting hypertrophic maturation. Taken together these results indicate that Dlx5 is a positive regulator of chondrocyte maturation during endochondral ossification, and suggest that it regulates the process at least in part by promoting the conversion of immature proliferating chondrocytes into hypertrophying chondrocytes; a critical step in the maturation process.
Chin
Hsian-Jean
HJ
Department of Genetics and Developmental Biology, University of Connecticut Health Center, School of Medicine, Farmington, Connecticut 06030, USA.
Fisher
Melanie C
MC
Li
Yingcui
Y
Ferrari
Deborah
D
Wang
Chi-Kuang Leo
CK
Lichtler
Alexander C
AC
Dealy
Caroline N
CN
Kosher
Robert A
RA
D000818:Animals; D001846:Bone Development / Q000235:genetics / Q000502:physiology*; D002454:Cell Differentiation / Q000235:genetics / Q000502:physiology*; D019902:Chondrocytes / Q000166:cytology* / Q000473:pathology; D024043:Collagen Type II / Q000235:genetics; D005121:Extremities / Q000033:anatomy & histology / Q000196:embryology*; D018398:Homeodomain Proteins / Q000235:genetics / Q000502:physiology*; D006984:Hypertrophy; D017880:Limb Deformities, Congenital / Q000196:embryology / Q000235:genetics / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic
C447413:Col2a1 protein, mouse; D024043:Collagen Type II; C501120:Dlx5 protein, mouse; D018398:Homeodomain Proteins