A crucial issue in limb development is how a correct set of precisely shaped digits forms in the digital plate. This process relies on patterning across the anterior-posterior axis of the limb bud, which is under the control of Sonic hedgehog emanating from the zone of polarizing activity. Recently, Sonic hedgehog function in the limb bud has been shown to have a dual character controlling both...

The development of vertebrate limbs is an excellent model to study patterning and growth regulation in embryogenesis (Capdevila and Izpisua Belmonte, 2001; Johnson and Tabin, 1997). The limb buds that result in morphologically distinct forelimbs and hindlimbs arise from the lateral plate mesoderm (LPM) at precise locations along the anteroposterior (AP) axis of the embryo. The induction of limb...

Signaling through the p38 mitogen-activated protein kinases (MAPKs) is essential for cartilage formation in primary cultures of limb mesenchyme. Here we show that, concurrent with a decrease in chondrogenesis, inhibition of p38 in limb bud cultures dramatically promotes muscle development. Specifically, treatment of primary limb bud cultures with p38 inhibitors increases the expression of myoge...

There is a crucial need to better understand the effects of low-doses of ionizing radiation in fetal models. Radiation-induced adaptive response (AR) was described in mouse embryos pre-exposed in utero to low-doses of X-rays, which exhibited lower apoptotic levels in the limb bud. We previously described AR-specific gene modulations in the mouse embryo. In this study, we evaluated the role of t...

We have created a 2D morphometric analysis of the developing mouse hindlimb bud. This analysis has provided two useful resources for the study of limb development. First, a temporally accurate numerical description of shape changes during normal mouse limb development. Second, a web-based morphometric staging system, which has the advantage of being easy to use, and with a reproducibility of ab...

Vertebrate limb outgrowth is driven by a positive feedback loop that involves Sonic hedgehog (Shh) and Gremlin1 (Grem1) in the posterior limb bud mesenchyme and Fibroblast growth factors (Fgfs) in the overlying epithelium. Proper spatio-temporal control of these signaling activities is required to avoid limb malformations such as polydactyly. Here we show that, in Tbx2-deficient hindlimbs, Shh/...

When it first appears at stage HH16, the wing bud is already polarized along the dorsoventral axis. To study the mechanisms leading to the establishment of its dorsoventral polarity, we decided to focus our attention on an earlier stage (HH13). Using the quail-chick chimera system, we first show that the presumptive wing mesoderm occupies the medial half of the somatopleure at the level of somi...

When polarizing mesoderm from the posterior border of the 4-day chick limb bud is placed adjacent to anterior limb mesoderm and ectodermal ridge, the anterior ridge thickens and mesodermal outgrowth ensues, resulting in supernumerary limb structures. This apposition of anterior and posterior limb tissues can be accomplished by cutting off the apical one third of the limb bud and reimplanting it...

Mutations in the murine limb deformity (ld) gene disrupt differentiation of the Apical Ectodermal Ridge (AER) and patterning of distal limb structures. However, initial outgrowth of the limb bud is not affected, suggesting that early and late functions of the AER are uncoupled. Similarly, activation of the 5' members of the HoxD gene cluster (Hoxd-11 to Hoxd-13) is not affected in ld mutant pos...

Vertebrate odd-skipped related genes (Osr) have an essential function during the formation of the intermediate mesoderm (IM) and the kidney structures derived from it. Here, we show that these genes are also crucial for limb bud formation in the adjacent lateral plate mesoderm (LPM). Reduction of zebrafish Osr function impairs fin development by the failure of tbx5a maintenance in the developin...