The apical ectodermal ridge is a timer for generating distal limb progenitors.
The apical ectodermal ridge (AER) is a transient embryonic structure essential for the induction, patterning and outgrowth of the vertebrate limb. However, the mechanism of AER function in limb skeletal patterning has remained unclear. In this study, we genetically ablated the AER by conditionally removing FGFR2 function and found that distal limb development failed in mutant mice. We showed that FGFR2 promotes survival of AER cells and interacts with Wnt/beta-catenin signaling during AER maintenance. Interestingly, cell proliferation and survival were not significantly reduced in the distal mesenchyme of mutant limb buds. We established Hoxa13 expression as an early marker of distal limb progenitors and discovered a dynamic morphogenetic process of distal limb development. We found that premature AER loss in mutant limb buds delayed generation of autopod progenitors, which in turn failed to reach a threshold number required to form a normal autopod. Taken together, we have uncovered a novel mechanism, whereby the AER regulates the number of autopod progenitors by determining the onset of their generation.
Lu
Pengfei
P
Department of Anatomy and Program in Developmental Biology, University of California at San Francisco, San Francisco, CA 94143-0452, USA. pengfei.lu@ucsf.edu
Yu
Ying
Y
Perdue
Yasmine
Y
Werb
Zena
Z
D000818:Animals; D017209:Apoptosis; D019521:Body Patterning; D049109:Cell Proliferation; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D004475:Ectoderm / Q000166:cytology / Q000196:embryology* / Q000378:metabolism; D053595:Embryonic Stem Cells / Q000166:cytology / Q000378:metabolism; D005121:Extremities / Q000196:embryology*; D005260:Female; D018507:Gene Expression Regulation, Developmental; D018398:Homeodomain Proteins / Q000235:genetics / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D008822:Mice, Transgenic; D008954:Models, Biological; D009154:Mutation; D011247:Pregnancy; D051497:Receptor, Fibroblast Growth Factor, Type 2 / Q000172:deficiency / Q000235:genetics; D015398:Signal Transduction; D051153:Wnt Proteins / Q000378:metabolism; D051176:beta Catenin / Q000378:metabolism
C495267:CTNNB1 protein, mouse; D004268:DNA-Binding Proteins; D018398:Homeodomain Proteins; C084119:MSX2 protein; D051153:Wnt Proteins; D051176:beta Catenin; C099959:homeobox protein HOXA13; C496354:Fgfr2 protein, mouse; D051497:Receptor, Fibroblast Growth Factor, Type 2