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Uncoupling skeletal and connective tissue patterning: conditional deletion in cartilage progenitors reveals cell-autonomous requirements for Lmx1b in dorsal-ventral limb patterning

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Date
2010
Authors
Li, Ying
Qiu, Qiong
Watson, Spenser S
Schweitzer, Ronen
Johnson, Randy L
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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 article
Subject
limb development
dorsal-ventral patterning
lmx1b
mouse
nail-patella syndrome
vertebrate limb
bud
expression
muscle
musculature
origin
fate
cre
developmental biology
Permalink
https://hdl.handle.net/10161/4174
Published Version (Please cite this version)
10.1242/dev.045237
Citation
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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