Extent of Duplication in Lower-Limb Malformations Suggests the Time of the Teratogenic Insult

PEDIATRICS ◽  
1993 ◽  
Vol 91 (2) ◽  
pp. 411-413
Author(s):  
David S. Packard ◽  
E. Mark Levinsohn ◽  
David R. Hootnick

Investigations of vertebrate limb development have suggested that a process called "specification" instructs the cells of the future limb as to which tissues they should form. This process proceeds in a wave-like manner, starting at the most proximal levels of the future limb and ending at its distal tip. Human limb specification probably occurs during the fourth and fifth weeks of development. It is proposed that human limb duplications result from errors of specification and, furthermore, that the more distal the duplication, the later the occurrence of the teratogenic event during the specification process. Therefore, among human lower limbs with duplications, one may be able to estimate the relative time of the teratogenic event by comparing the levels at which the duplications occur.

Development ◽  
1998 ◽  
Vol 125 (22) ◽  
pp. 4417-4425 ◽  
Author(s):  
M. Takahashi ◽  
K. Tamura ◽  
D. Buscher ◽  
H. Masuya ◽  
S. Yonei-Tamura ◽  
...  

We have determined that Strong's Luxoid (lstJ) [corrected] mice have a 16 bp deletion in the homeobox region of the Alx-4 gene. This deletion, which leads to a frame shift and a truncation of the Alx-4 protein, could cause the polydactyly phenotype observed in lstJ [corrected] mice. We have cloned the chick homologue of Alx-4 and investigated its expression during limb outgrowth. Chick Alx-4 displays an expression pattern complementary to that of shh, a mediator of polarizing activity in the limb bud. Local application of Sonic hedgehog (Shh) and Fibroblast Growth Factor (FGF), in addition to ectodermal apical ridge removal experiments suggest the existence of a negative feedback loop between Alx-4 and Shh during limb outgrowth. Analysis of polydactylous mutants indicate that the interaction between Alx-4 and Shh is independent of Gli3, a negative regulator of Shh in the limb. Our data suggest the existence of a negative feedback loop between Alx-4 and Shh during vertebrate limb outgrowth.


Development ◽  
2000 ◽  
Vol 127 (19) ◽  
pp. 4169-4178 ◽  
Author(s):  
H. Grandel ◽  
B.W. Draper ◽  
S. Schulte-Merker

Classical embryological studies have implied the existence of an apical ectodermal maintenance factor (AEMF) that sustains signaling from the apical ectodermal ridge (AER) during vertebrate limb development. Recent evidence suggests that AEMF activity is composed of different signals involving both a sonic hedgehog (Shh) signal and a fibroblast growth factor 10 (Fgf10) signal from the mesenchyme. In this study we show that the product of the dackel (dak) gene is one of the components that acts in the epidermis of the zebrafish pectoral fin bud to maintain signaling from the apical fold, which is homologous to the AER of tetrapods. dak acts synergistically with Shh to induce fgf4 and fgf8 expression but independently of Shh in promoting apical fold morphogenesis. The failure of dak mutant fin buds to progress from the initial fin induction phase to the autonomous outgrowth phase causes loss of both AER and Shh activity, and subsequently results in a proximodistal truncation of the fin, similar to the result obtained by ridge ablation experiments in the chicken. Further analysis of the dak mutant phenotype indicates that the activity of the transcription factor engrailed 1 (En1) in the ventral non-ridge ectoderm also depends on a maintenance signal probably provided by the ridge. This result uncovers a new interaction between the AER and the dorsoventral organizer in the zebrafish pectoral fin bud.


Nature ◽  
1996 ◽  
Vol 379 (6568) ◽  
pp. 848-848 ◽  
Author(s):  
Astrid Vogel ◽  
Concepción Rodriguez ◽  
Wayne Warnken ◽  
Juan Carlos Izpisúa Belmonte

Sensors ◽  
2019 ◽  
Vol 19 (22) ◽  
pp. 5042
Author(s):  
Adriana Comanescu ◽  
Ileana Dugaesescu ◽  
Doru Boblea ◽  
Liviu Ungureanu

In order to develop multifunctional medical recovery and monitoring equipment for the human lower limb, a new original mechanical structure with three degrees mobility has been created for the leg sagittal model. This mechanism is integrated in the equipment and includes elements that have similar functions to the different anatomic parts (femur, median part), leg, and foot. The independent relative rotation motion between the previously mentioned anatomic parts is ensured. The femur may have an oscillation rotation of about 100° relative to the trunk. The median part (leg) alternatively rotates 150° relative to the superior segment. The lower part (foot) is initially placed at 90° relative to the median part and may have an alternative rotation of 25°. Depending on a patient’s medical needs and their recovery progress, device sensors provide varying angular amplitude of different segments of the human limb. Moreover, the mechanism may actuate either anatomic leg segment, two parts, or all of them.


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