TY - JOUR
T1 - Tbx genes specify posterior digit identity through Shh and BMP signaling
AU - Suzuki, Takayuki
AU - Takeuchi, Jun
AU - Koshiba-Takeuchi, Kazuko
AU - Ogura, Toshihiko
N1 - Funding Information:
We thank C.E. Campbell and C. Tabin for probes. We also thank J.F. Fallon for helpful comments and critical reading. This work was supported by a Grant-in-Aid for Scientific Research on Priority Areas from the Ministry of Education, Science Sports and Culture of Japan (T.O.), by a Creative Basic Research grant from the Ministry of Education, Science Sports and Culture of Japan (T.O.), and by the Toray Science Foundation (T.O.). This work was also funded in part by the Dan Charitable Trust Fund for Research in the Biological Sciences (J.K.T.) and The Mochida Memorial Foundation for Medical and Pharmaceutical Research (K.K.-T.). J.K.T. was supported by a JSPS Research Fellowship for Young Scientists. T.S. is also supported by a JSPS Research Fellowship for Young Scientists.
PY - 2004/1
Y1 - 2004/1
N2 - Despite extensive studies on the anterior-posterior (AP) axis formation of limb buds, mechanisms that specify digit identities along the AP axis remain obscure. Using the four-digit chick leg as a model, we report here that Tbx2 and Tbx3 specify the digit identities of digits IV and III, respectively. Misexpression of Tbx2 and Tbx3 induced posterior homeotic transformation of digit III to digit IV and digit II to digit III, respectively. Conversely, misexpression of their mutants VP16ΔTbx2 and VP16ΔTbx3 induced anterior transformation. In both cases, alterations in the expression of several markers (e.g., BMP2, Shh, and HoxD genes) were observed. In addition, Tbx2 and Tbx3 rescued Noggin-mediated inhibition of interdigital BMP signaling, signaling which is pivotal in establishing digit identities. Hence, we conclude that Tbx3 specifies digit III, and the combination of Tbx2 and Tbx3 specifies digit IV, acting together with the interdigital BMP signaling cascade.
AB - Despite extensive studies on the anterior-posterior (AP) axis formation of limb buds, mechanisms that specify digit identities along the AP axis remain obscure. Using the four-digit chick leg as a model, we report here that Tbx2 and Tbx3 specify the digit identities of digits IV and III, respectively. Misexpression of Tbx2 and Tbx3 induced posterior homeotic transformation of digit III to digit IV and digit II to digit III, respectively. Conversely, misexpression of their mutants VP16ΔTbx2 and VP16ΔTbx3 induced anterior transformation. In both cases, alterations in the expression of several markers (e.g., BMP2, Shh, and HoxD genes) were observed. In addition, Tbx2 and Tbx3 rescued Noggin-mediated inhibition of interdigital BMP signaling, signaling which is pivotal in establishing digit identities. Hence, we conclude that Tbx3 specifies digit III, and the combination of Tbx2 and Tbx3 specifies digit IV, acting together with the interdigital BMP signaling cascade.
UR - http://www.scopus.com/inward/record.url?scp=0345873191&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0345873191&partnerID=8YFLogxK
U2 - 10.1016/S1534-5807(03)00401-5
DO - 10.1016/S1534-5807(03)00401-5
M3 - Article
C2 - 14723846
AN - SCOPUS:0345873191
SN - 1534-5807
VL - 6
SP - 43
EP - 53
JO - Developmental Cell
JF - Developmental Cell
IS - 1
ER -