spacer gif spacer gif spacer gif spacer gif spacer gif
QUICK SEARCH:   [advanced]


spacer gif
     Home     Help     Feedback     Subscriptions     Archive     Search     Table of Contents    

First published online 23 February 2005
doi: 10.1242/dev.01735

Development 132, 1601-1610 (2005)
Published by The Company of Biologists 2005
This Article
Right arrow Summary Freely available
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrow reprints & permissions
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Kuijper, S.
Right arrow Articles by Meijlink, F.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Kuijper, S.
Right arrow Articles by Meijlink, F.
Social Bookmarking
Add to CiteULike   Add to Complore   Add to Connotea   Add to Del.icio.us   Add to Digg   Add to Reddit   Add to Technorati   Add to Twitter  
What's this?

Genetics of shoulder girdle formation: roles of Tbx15 and aristaless-like genes

Sanne Kuijper1, Annemiek Beverdam1,*, Carla Kroon1, Antje Brouwer1, Sophie Candille2, Gregory Barsh2 and Frits Meijlink1,{dagger}

1 Hubrecht Laboratory, The Netherlands Institute for Developmental Biology, Uppsalalaan 8, 3584CT Utrecht, The Netherlands
2 Departments of Genetics and Pediatrics, Stanford University School of Medicine, Stanford, CA, USA



View larger version (80K):

[in a new window]
  		Fig. 1. Expression of Tbx15 at E10.5. (A) Expression of Tbx15 in wild-type forelimb bud at E10.5. (B) Expression of Tbx15 in hindlimb bud at E11.5. (C) Pax1 expression in wild-type forelimb bud at E10.5. Note that the expression of Pax1 in the shoulder-forming region is complementary with that of Tbx15. (D,E) Alx4 expression in wild-type (D) and Gli3–/– (E) forelimb buds at E10.5. In Gli3–/– limb buds, Alx4 expression is downregulated in the distal part of its normal expression domain. (F-I) Expression of Emx2 in wild-type (F,H), Alx4–/–/Cart1–/– (G) and Gli3–/–/Tbx15–/– (I) forelimb buds at E10.5. (J) Tbx15 in situ hybridization on a wild-type sagittal section at E10.5. Black arrow indicates expression in notochord and surrounding mesenchyme. (K,L) Tbx15 in situ hybridization on wild-type transverse sections at E10.5. (K) Black arrowhead shows expression of Tbx15 in lateral cranial mesenchyme. (L) Higher magnification of section shown in K showing expression of Tbx15 in notochord (black arrow) and surrounding mesenchyme. a, atrium; m, mandibular component; mx, maxillary component of first branchial arch; v, ventricle.

 


View larger version (92K):

[in a new window]
  		Fig. 2. Skeletal abnormalities of Tbx15 mutants. Alcian Blue and Alizarin Red staining of newborn and E13.5 wild-type and Tbx15 mutants. (A) Newborn Tbx15 mutants have a foramen in the blade of the scapula and the humerus is shorter than in wild type. (B,C) Alcian Blue staining of E13.5 wild-type (B) and Tbx15 mutant (C) shoulder girdle. At this stage the phenotype is already present. (D) Abnormalities of the caudal posterior aspect of vertebrae in newborn Tbx15 mutants. Arrow indicates ectopic cartilage in the atlas of Tbx15 mutant; arrowhead indicates the place were the dens of the axis is missing. (E,F) Cranial base of a newborn wild-type (E) and Tbx15–/– (F) skull. The Tbx15 mutant skull is shorter and narrower than the wild type, and the basioccipital bone (B) is narrow when compared with wild type; also the inner ear (I) has an abnormal medial and caudal position.

 


View larger version (95K):

[in a new window]
  		Fig. 3. The scapular blade is severely affected in Tbx15/Gli3 and Alx4/Cart1/Tbx15 compound mutants. (A-N) Skeletal staining of the shoulder girdle of E16.5 embryos. Black arrowheads (B,D,F,I,K-N) indicate the reduced acromion in Tbx15/Gli3 and Alx4/Cart1/Tbx15 mutants; white arrowheads (C) indicate the indentations in the scapular blade of Gli3 mutants; black arrows (H-J,M) indicate the reduction of the anterior part of the scapular blade in Alx3/Alx4, Alx4/Cart1 and Alx4/Cart1/Tbx15 compound mutants. Note the severely reduced acromion and the remaining posterior part of the scapular blade in the Alx4–/–Cart1–/–Tbx15–/– mutant shoulder girdle (N). (O,P) Side view of the intact skeleton of wild-type (O) and Alx4–/–/Cart1–/–/Tbx15–/– (P) embryos at E16.5. Green arrowhead in O indicates the clavicle, which is missing in Alx4/Cart1/Tbx15 mutants (green arrowhead in P). Red arrowhead indicates the scapula; black arrowhead indicates the acromion. (Q-V) Clavicles of Alx3/Alx4/Cart1/Tbx15 compound mutants. The clavicle size is slightly reduced in Alx3/Alx4 double mutants (T), but only a small remnant of the clavicle is visible in Alx4/Cart1 (U) and Alx4–/–Cart1–/–Tbx15+/– mutants (V). (W) Schematic representation of the elements of the shoulder girdle. (X) Schematic representation of the distinct functions of Alx4/Cart1 (red), Gli3 (blue) and Tbx15 (green) during shoulder girdle development. Alx4, Cart1 and Tbx15 (red/green) have functions during clavicle development.

 


View larger version (106K):

[in a new window]
  		Fig. 4. Pelvic abnormalities in Alx4 mutants. (A-E) Skeletal staining of pelvic girdles of E16.5 embryos. Black arrowhead indicates a reduction or absence of the pubic bone in Alx4 (B), Alx3/Alx4 (C), Alx4/Cart1 (D) mutants, whereas the pelvic girdle in Tbx15 mutants (E) was not affected.

 


View larger version (70K):

[in a new window]
  		Fig. 5. Gene regulation in Alx4, Cart1, Gli3 and Tbx15 compound mutants. (A-D) Pax1 expression in E10.5 wild-type (A), Tbx15–/– (B), Gli3–/– (C) and Tbx15/Gli3 double mutant (D) forelimb buds. Note the downregulation of Pax1 expression in the mutants. (E-L) Pax1 expression in E10.75 wild-type (E,I), Alx4–/– (F), Cart1–/– (G), Alx4+/–/Cart1–/– (J) and Alx4–/–/Cart1–/– (H,K,L) forelimb buds. (E-H) Dorsal views of the limb buds. Note the downregulation of Pax1 in Alx4/Cart1 compound mutants (H). (I-L) Ventral view of the limb buds. Yellow arrowhead indicates the shift of Pax1 expression in Alx4+/–/Cart1–/– (J) and Alx4–/–/Cart1–/– (K,L) mutants. (M-P) Pax1 expression in wild-type (M,O) and Alx4/Cart1 mutant (N,P) fore- and hindlimb (HL) buds at E11.5. Yellow arrowhead (N,P) indicates the shift of Pax1 expression. (Q-T) In situ hybridization on serial transversal sections at E10.5 of wild-type (Q,S) and Alx4/Cart1 mutant (R,T) embryos. (Q,R) Pax1 expression is downregulated in Alx4/Cart1 mutants. (S,T) Pax3 is abnormally expressed in the mesenchyme just adjacent to the surface ectoderm in Alx4/Cart1 mutants (black arrow in T). (U,V) Whole-mount in situ hybridization with Pax3 probe of E10.5 wild-type (U) and Alx4/Cart1 mutant (V) limb buds. Red arrowhead (V) indicates Pax3 expression that is shifted towards the antero-proximal region of the limb bud. (W,X) Expression of Scleraxis (Scx) in E10.5 wild-type (W) and Alx4/Cart1 mutant (X) limb buds. Green arrowhead (X) indiactes the shift of Scx expression in the Alx4/Cart1 mutant. (Y) Schematic representation of the expression patterns of Pax1, Pax3 and Scleraxis in wild type, and in Alx4/Cart1 and Tbx15/Gli3 compound mutants.

 

Add to CiteULike CiteULike   Add to Complore Complore   Add to Connotea Connotea   Add to Del.icio.us Del.icio.us   Add to Digg Digg   Add to Reddit Reddit   Add to Technorati Technorati   Add to Twitter Twitter    What's this?



© The Company of Biologists Ltd 2005