Uncoupling skeletal and connective tissue patterning: conditional deletion in cartilage progenitors reveals cell-autonomous requirements for Lmx1b in dorsal-ventral limb patterning
Abstract
Integration of muscle, connective tissue and skeletal patterning during development
is essential for proper functioning of the musculoskeletal system. How this integration
is achieved is poorly understood. There is ample evidence suggesting that skeletal
pattern is programmed autonomously, whereas muscle pattern is, for the most part,
programmed non-cell-autonomously. Connective tissues depend upon both muscle and skeletal
tissues for their proper survival and development. Here, we employed a novel approach
to dissect the coordination of musculoskeletal patterning during mouse limb development.
Using both conditional gain- and loss-of-function approaches, we selectively deleted
or activated the LIM-homeodomain transcription factor Lmx1b in skeletal progenitors
using a Sox9-Cre knock-in allele. As Lmx1b is both necessary and sufficient to specify
dorsal pattern, this approach allowed us to investigate the effect of selectively
deleting or activating Lmx1b in skeletal progenitors on muscle, connective and skeletal
tissues during limb development. Our results indicate that whereas Lmx1b activity
is required autonomously in skeletal progenitors to direct dorsal pattern, loss or
gain of Lmx1b activity in skeletal progenitors has no effect on muscle or connective
tissue patterning. Hence, we show for the first time that skeletal and connective
tissue patterning can be uncoupled, indicating a degree of autonomy in the formation
of the musculoskeletal system.
Type
Other articleSubject
limb developmentdorsal-ventral patterning
lmx1b
mouse
nail-patella syndrome
vertebrate limb
bud
expression
muscle
musculature
origin
fate
cre
developmental biology
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https://hdl.handle.net/10161/4174Published Version (Please cite this version)
10.1242/dev.045237Citation
Li,Ying;Qiu,Qiong;Watson,Spenser S.;Schweitzer,Ronen;Johnson,Randy L.. 2010. Uncoupling
skeletal and connective tissue patterning: conditional deletion in cartilage progenitors
reveals cell-autonomous requirements for Lmx1b in dorsal-ventral limb patterning.
Development 137(7): 1181-1188.
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