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Fate map of mouse ventral limb ectoderm and the apical ectodermal ridge
Qiuxia Guo1, Cynthia Loomis, Alexandra L Joyner
1Howard Hughes Medical Institute and Developmental Genetics Program, Skirball Institute of Biomolecular Medicine, New York University School of Medicine, 540 First Avenue, New York, NY 10016, USA.
Developmental Biology
|November 19, 2003
Summary
Mouse limb development involves a specialized structure called the apical ectodermal ridge (AER). New research reveals AER cells are transient, disappearing by birth, while preAER cells contribute to paw ectoderm.
Area of Science:
- Developmental Biology
- Molecular Biology
- Genetics
Background:
- The apical ectodermal ridge (AER) is crucial for limb outgrowth, forming a thickened epithelium at the limb tip.
- AER formation involves gene expression changes and cell thickening, visible from embryonic day 10.5 to 13.5 in mice.
- Previous studies suggested AER cells and their descendants remain within the AER, with some preAER cells contributing to ventral ectoderm.
Purpose of the Study:
- To investigate the long-term fate of pre-apical ectodermal ridge (preAER) cells and mature AER cells during mouse limb development.
- To clarify the contribution of preAER cells to the ventral ectoderm and the ultimate fate of AER-derived cells.
- To understand the cellular mechanisms underlying AER formation and ventral ectoderm partitioning.
Main Methods:
- Utilized an inducible CreER/loxP fate mapping system in mice.
- Employed a CreER transgene with Msx2 regulatory sequences specific to the developing AER.
- Marked preAER cells at different developmental stages (stage 2 and post-onset of preAER gene expression) and mature AER cells.
Main Results:
- Marking preAER cells at stage 2 showed their descendants primarily form the ventral ectoderm of the paw by embryonic day 16.5.
- Marking preAER cells after preAER gene expression onset resulted in similar paw ventral ectoderm marking, plus the AER.
- Long-term fate mapping demonstrated that AER-derived cells are gradually lost after embryonic day 12.5, with none remaining by birth.
- A distinct dorsal/ventral border is maintained in paw ectoderm, with the nail bed's edge marking the distal boundary.
Conclusions:
- The apical ectodermal ridge (AER) is a distinct but transient compartment during mouse limb development.
- Pre-apical ectodermal ridge (preAER) cells contribute significantly to the ventral ectoderm of the developing paw.
- These findings reveal novel cellular dynamics in AER formation and ventral ectoderm patterning in the mouse limb.