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How to make a limb: developmental paradigms
Author(s) -
Niswander Lee Ann
Publication year - 2008
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.22.1_supplement.234.4
Subject(s) - mesenchyme , limb development , limb bud , biology , embryonic stem cell , anatomy , zone of polarizing activity , process (computing) , cartilage , vertebrate , neuroscience , cell fate determination , microbiology and biotechnology , evolutionary biology , mesoderm , gene , genetics , embryo , computer science , transcription factor , operating system
The embryonic vertebrate limb is a classic paradigm for the study of pattern formation, cell growth and death, and skeletal formation. Our understanding of the molecular signals that regulate limb patterning is relatively complete. However, many questions remain as to how these signals are interpreted and translated into skeletal elements that are adapted to the needs of each animal on land, sea and air. Outstanding questions in patterning and skeletal formation include how and when are limb cells specified and acquire distinct cell fates in order to contribute to specific skeletal elements and what are the cellular and molecular mechanisms that lead to the establishment of the skeletal elements of the correct size and shape? Our work is driven forward by two approaches. The first is the creation of mouse mutants with defects in limb development. We then clone the responsible gene that is mutated and discover its mechanism of action. The second approach uses a new imaging method to watch in real time as the limb mesenchyme undergoes the early steps of cartilage formation. We then combine this with the study of limb mesenchyme from mouse mutants to begin to understand the cell behaviors that are affected in mutants with too many digits, too few digits, or defects in cartilage formation. Furthermore, we have used our knowledge of limb development in models organisms, the mouse and chick, to begin to unravel the molecular mechanisms that underlie evolutionary change in the bat.