Two lineage boundaries coordinate vertebrate apical ectodermal ridge formation

Citation
Ra. Kimmel et al., Two lineage boundaries coordinate vertebrate apical ectodermal ridge formation, GENE DEV, 14(11), 2000, pp. 1377-1389
Citations number
63
Language
INGLESE
art.tipo
Article
Categorie Soggetti
Cell & Developmental Biology
Journal title
GENES & DEVELOPMENT
ISSN journal
0890-9369 → ACNP
Volume
14
Issue
11
Year of publication
2000
Pages
1377 - 1389
Database
ISI
SICI code
0890-9369(20000601)14:11<1377:TLBCVA>2.0.ZU;2-1
Abstract
Proximal-distal outgrowth of the vertebrate limb bud is regulated by the ap ical ectodermal ridge (AER), which forms at an invariant position along the dorsal-ventral (D/V) axis of the embryo. We have studied the genetic and c ellular events that regulate AER formation in the mouse. In contrast to imp lications from previous studies in chick, we identified two distinct lineag e boundaries in mouse ectoderm prior to limb bud outgrowth using a Cre/loxP -based fate-mapping approach and a novel retroviral cell-labeling technique . One border is transient and at the limit of expression of the ventral gen e En1, which corresponds to the D/V midline of the AER, and the second bord er corresponds to the dorsal AER margin. Labeling of AER precursors using a n inducible Cre showed that not all cells that initially express AER genes form the AER, indicating that signaling is required to maintain an AER phen otype. Misexpression of En1 at moderate Levels specifically in the dorsal A ER of transgenic mice was found to produce dorsally shifted AER fragments, whereas high levels of En1 abolished AER formation. In both cases, the dors al gene Wnt7a was repressed in cells adjacent to the En1-expressing cells, demonstrating that signaling regulated by EN1 occurs across the D/V border. Finally, fate mapping of AER domains in these mutants showed that En1 play s a part in positioning and maintaining the two lineage borders.