Display Settings:

Items per page

Results: 10

1.
Figure 5

Figure 5. From: The transcription factor Sox9 has essential roles in successive steps of the chondrocyte differentiation pathway and is required for expression of Sox5 and Sox6.

Analysis of apoptosis in Sox9flox/flox; Prx1–Cre mice. TUNEL (a,d), immunohistochemistry of Bax (b,e) and cleaved caspase 3 (c,f), and in situ hybridization of Bmp2 (g,j), Noggin (h,k), and Chordin (i,l) in limb buds of E13.5 wild-type and mutant embryos, respectively. The arrows indicate the expression of Bmp2 in the vicinity of interdigital spaces. The arrowheads indicate the expression of Chordin.

Haruhiko Akiyama, et al. Genes Dev. 2002 November 1;16(21):2813-2828.
2.
Figure 4

Figure 4. From: The transcription factor Sox9 has essential roles in successive steps of the chondrocyte differentiation pathway and is required for expression of Sox5 and Sox6.

Expression of markers of limb patterning in Sox9flox/flox; Prx1–Cre mice. The normal expression in limb buds of E11.5 (A) and E12.5 (B) mutant embryos of Fgf8, Shh, Lmx1b, En1, Msx1, HoxD12, HoxD13, Prx1, and Twist revealed no patterning defects in the mutant limb buds. A, anterior; P, posterior; V, ventral; D, dorsal. The arrows indicate the expression domain of En1.

Haruhiko Akiyama, et al. Genes Dev. 2002 November 1;16(21):2813-2828.
3.
Figure 6

Figure 6. From: The transcription factor Sox9 has essential roles in successive steps of the chondrocyte differentiation pathway and is required for expression of Sox5 and Sox6.

Severe, generalized chondrodysplasia in Sox9flox/flox; Col2a1–Cre mice. (A) Gross appearance of E18.5 embryos. (B) Skeletons of E17.5 mice stained by alcian blue followed by alizarin red. Mutant embryos were characterized by a very severe and generalized chondrodysplasia. (C) Expression of Sox9 protein in metacarpals of E12.5, E13.5, and E15.5 wild-type and mutant embryos, respectively. The inactivation of Sox9 occurred over a short window of time starting in condensed mesenchymal cells.

Haruhiko Akiyama, et al. Genes Dev. 2002 November 1;16(21):2813-2828.
4.
Figure 9

Figure 9. From: The transcription factor Sox9 has essential roles in successive steps of the chondrocyte differentiation pathway and is required for expression of Sox5 and Sox6.

Expression of markers of chondrocytes, Ihh/Pthrp regulatory signaling molecules, and markers of osteoblast differentiation in Sox9flox/flox; Col2a1–Cre mice. (A) Expression of Col2a1, Aggrecan, and Comp, but not Col10a1 was dramatically down-regulated in E15.5 mutant metacarpals. (B) RNA in situ hybridization showed down-regulation of Pthrp, PPR, Ihh, and Ptc1 in E15.5 mutant metacarpals. (C) Expression in radius of E15.5 mutant mice of Bsp, Osteopontin, Osteocalcin, and Runx2 revealed normal osteoblast differentiation. P, proliferating; PH, prehypertrophic; H, hypertrophic.

Haruhiko Akiyama, et al. Genes Dev. 2002 November 1;16(21):2813-2828.
5.
Figure 8

Figure 8. From: The transcription factor Sox9 has essential roles in successive steps of the chondrocyte differentiation pathway and is required for expression of Sox5 and Sox6.

In situ hybridization analyses of markers of joint formation and of downstream genes of Sox9 in chondrocytes. (A) Alcian blue and nuclear fast red staining and RNA in situ hybridization of Gdf5, Noggin, and Wnt14 in carpal cartilage primordia of E15.5 wild-type and mutant mice. The arrows indicate fusion of carpal bones. (B) Sox5 and Sox6 are downstream genes of Sox9 in chondrocytes. RNA in situ hybridization showed absence of expression of Sox5 and Sox6 in chondrocytes of E12.5 Sox9flox/flox; Col2a1–Cre mice.

Haruhiko Akiyama, et al. Genes Dev. 2002 November 1;16(21):2813-2828.
6.
Figure 3

Figure 3. From: The transcription factor Sox9 has essential roles in successive steps of the chondrocyte differentiation pathway and is required for expression of Sox5 and Sox6.

Expression of early markers of osteoblast differentiation and chondrogenic mesenchymal condensations in limb buds of Sox9flox/flox; Prx1–Cre mice. (A) The limb buds of E12.5 wild-type and mutant embryos were hybridized with the Runx2 probe. Runx2 RNA was not detected in the mutant limb buds. (B) The limb buds of E15.5 wild-type and mutant embryos were hybridized with Bsp or Runx2 probes. Bsp and Runx2 transcripts were not detectable in mutant limb mesenchymal tissues. (C) Whole-mount RNA in situ hybridization showed lack of expression of Col2a1 (a,d), Sox5 (b,e), and Sox6 (c,f) in E12.5 mutant limb buds.

Haruhiko Akiyama, et al. Genes Dev. 2002 November 1;16(21):2813-2828.
7.
Figure 10

Figure 10. From: The transcription factor Sox9 has essential roles in successive steps of the chondrocyte differentiation pathway and is required for expression of Sox5 and Sox6.

Functions of Sox9 in the successive steps of the chondrocyte differentiation pathway during endochondral bone formation. Sox9 commits undifferentiated mesenchymal cells in the lateral plate mesoderm to osteochondroprogenitors. Sox9 is also needed for chondrogenic mesenchymal condensation, subsequent overt chondrocyte differentiation, and normal chondrocyte proliferation. Overt chondrocyte differentiation and normal chondrocyte proliferation are at least in part mediated by Sox5 and Sox6, the expression of which requires Sox9. Finally, Sox9 inhibits transition of proliferating chondrocytes to hypertrophy. It is also possible that Sox5 and Sox6 participate in inhibiting this last step.

Haruhiko Akiyama, et al. Genes Dev. 2002 November 1;16(21):2813-2828.
8.
Figure 7

Figure 7. From: The transcription factor Sox9 has essential roles in successive steps of the chondrocyte differentiation pathway and is required for expression of Sox5 and Sox6.

Histological analysis in Sox9flox/flox; Col2a1–Cre mice. (A,B) Alcian blue and nuclear fast-red staining of metacarpals (A) and radius (B) during chondrocytic differentiation showed abnormal endochondral bone formation. The arrows indicate a thin layer of periosteum-like cells surrounding bone trabeculae and hypertrophic chondrocytes (B, g,h). A boxed region in B, h is shown at a high magnification as B, i. (C) Staining by von Kossa's method visualized mineral deposition in radius of E15.5 wild-type and mutant mice. (D) PCNA staining showed only a few PCNA-positive cells (brown nuclei) in metacarpals of E15.5 mutant embryos.

Haruhiko Akiyama, et al. Genes Dev. 2002 November 1;16(21):2813-2828.
9.
Figure 2

Figure 2. From: The transcription factor Sox9 has essential roles in successive steps of the chondrocyte differentiation pathway and is required for expression of Sox5 and Sox6.

Analysis of skeletal phenotypes in Sox9flox/flox; Prx1–Cre mice. (A) Gross appearance of newborn mice. Mutant newborns had very short limbs. (B) Skeletons of newborn mice stained by alcian blue followed by alizarin red. Cartilage and bone in the mutant limbs were completely absent. (C) Histological analysis of limb buds stained by hematoxylin and Treosin at 11.5 dpc (a,b), 12.5 dpc (c,d), and 13.5 dpc (g,h). Mutant limb buds had no discernible chondrogenic mesenchymal condensations at 12.5 dpc (c,d). Boxed regions at 12.5 dpc are shown at a high magnification (e,f). The arrows indicate chondrogenic mesenchymal condensations. (D) Morphological analysis of limb buds by scanning electron microscope. In the mutant limb buds, no distinct digit formation was observed, and the outgrowth of the mutant limb buds was arrested. (E) Micromass culture of dissociated mutant mesenchymal cells shows no alcian-blue positive cartilaginous nodules 7 d after plating. (F) Expression of Myogenin RNA in limb buds of E15.5 wild-type and mutant embryos. Myogenin-positive cells were present in the mutant limb buds.

Haruhiko Akiyama, et al. Genes Dev. 2002 November 1;16(21):2813-2828.
10.
Figure 1

Figure 1. From: The transcription factor Sox9 has essential roles in successive steps of the chondrocyte differentiation pathway and is required for expression of Sox5 and Sox6.

Targeting strategy for conditional inactivation of the gene for Sox9. (A) Structure of the genomic Sox9 locus, targeting vector, and the homologous recombined allele. Exons are depicted as closed boxes, and intronic sequences are shown as solid lines. The Neo cassette is depicted as an open box. Forward and reverse primers used for PCR genotyping for floxdel alleles are shown as arrowheads. DNA fragments revealed in Southern analysis are indicated as arrows with the restriction enzymes and the probe. B, BamHI; P, PstI; X, XbaI; E, EagI; S, SspI. (B) Southern blot analysis of fetal genomic DNA. Genomic DNA isolated from the skin of wild-type, Sox9flox/wt; Cre, and Sox9flox/flox; Cre was digested with BamHI and then hybridized with the 3′ probe. The wild-type and floxed alleles were detected as 13-kb and 7.2-kb fragments, respectively. (C) PCR genotyping of Cre transgenes and floxdel alleles. (D,E) Expression of Sox9 mRNA (in situ hybridization, D) and Sox9 protein (immunohistochemistry, E) in limb buds of E12.5 wild-type and Sox9flox/flox; Prx1–Cre embryos. Both Sox9 mRNA and Sox9 protein were not detected in mutant limb buds.

Haruhiko Akiyama, et al. Genes Dev. 2002 November 1;16(21):2813-2828.

Display Settings:

Items per page

Supplemental Content

Recent activity

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

See more...
Write to the Help Desk