Abstract
A major goal of biology has been to understand the developmental mechanisms behind evolutionary trends. This has led to a growing interest in studying the molecular basis of the evolution of developmental programs such as those mediating the diversification of tetrapod limbs. Over the last 10 y, it has become clear that the genes and general developmental programs used to build a limb are strongly conserved among widely disparate species. This finding suggests that altered regulation of the timing and locations of developmental events may be responsible for the morphologic variation observed among some species. However, genetic analyses of the regulatory regions of genes controlling vertebrate developmental programs are very limited. Characterization of the genetic basis of human birth defects of the limb provides an opportunity to dissect the developmental programs used to modify the architecture of the hominoid limb. This may allow us to assess the relative contributions of altered gene regulation to morphologic variation among species and reconstruct the evolutionary history of the hominid limb. Such insight is also important because morphologic differences in the hominid upper limb have been correlated with the use of tools, and tool making is often regarded as the milestone that marked the emergence of the genus Homo.
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Abbreviations
- A/P :
-
anterior/posterior
- AER :
-
apical ectodermal ridge
- D/V :
-
dorsal/ventral
- ECP :
-
ectrodactyly with cleft lip/palate
- EEC :
-
ectrodactyly with ectodermal dysplasia
- En-1 :
-
Engrailed-1
- FGF :
-
fibroblast growth factor
- GLI :
-
glioma-associated oncogene
- HFGS :
-
hand-foot-genital syndrome
- HOS :
-
Holt-Oram syndrome
- HOX :
-
homeobox
- Ldh-B :
-
lactate dehydrogenase B
- P/D :
-
proximal/distal
- PZ :
-
progress zone
- r-Fng :
-
radical fringe
- SHFM :
-
split-hand/foot malformation
- Shh :
-
Sonic hedgehog
- SPD :
-
synpolydactyly
- TBX :
-
T-box
- UMS :
-
ulnar-mammary syndrome
- Wnt :
-
Wingless-type MMTV integration site family member
- ZPA :
-
zone of polarizing activity
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Acknowledgements
The authors thank the lab members and collaborators for many interesting conversations that clarified issues. We apologize to all of those whose work was not cited.
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Supported by Shriners Hospitals for Children Grant SHC 9510 (to M.B.), General Clinical Research Center at the University of Utah Grant PHS MO1-00064, and a grant from the Primary Children's Foundation (to M.B.).
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Bamshad, M., Watkins, W., Dixon, M. et al. Reconstructing the History of Human Limb Development: Lessons from Birth Defects. Pediatr Res 45, 291–299 (1999). https://doi.org/10.1203/00006450-199903000-00001
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DOI: https://doi.org/10.1203/00006450-199903000-00001
