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PMID:22071103
| Citation |
Duboc, V and Logan, MP (2011) Pitx1 is necessary for normal initiation of hindlimb outgrowth through regulation of Tbx4 expression and shapes hindlimb morphologies via targeted growth control. Development 138:5301-9 |
|---|---|
| Abstract |
The forelimbs and hindlimbs of vertebrates are morphologically distinct. Pitx1, expressed in the hindlimb bud mesenchyme, is required for the formation of hindlimb characteristics and produces hindlimb-like morphologies when misexpressed in forelimbs. Pitx1 is also necessary for normal expression of Tbx4, a transcription factor required for normal hindlimb development. Despite the importance of this protein in these processes, little is known about its mechanism of action. Using a transgenic gene replacement strategy in a Pitx1 mutant mouse, we have uncoupled two discrete functions of Pitx1. We show that, firstly, this protein influences hindlimb outgrowth by regulating Tbx4 expression levels and that, subsequently, it shapes hindlimb bone and soft tissue morphology independently of Tbx4. We provide the first description of how Pitx1 sculpts the forming hindlimb skeleton by localised modulation of the growth rate of discrete elements. |
| Links |
PubMed PMC3222209 Online version:10.1242/dev.074153 |
| Keywords |
Animals; Body Patterning; Bone Development; Gene Expression Regulation, Developmental; Hindlimb/growth & development; Hindlimb/metabolism; Mesoderm/growth & development; Mesoderm/metabolism; Mice; Mice, Transgenic; Paired Box Transcription Factors/metabolism; T-Box Domain Proteins/metabolism |
| edit table |
Significance
Annotations
| Gene product | Qualifier | GO Term | Evidence Code | with/from | Aspect | Extension | Notes | Status |
|---|---|---|---|---|---|---|---|---|
| GO:0060415: muscle tissue morphogenesis |
ECO:0000315: |
P |
Figure 3 (C and D) show that extensor digitorum brevis muscle formation is rescued by Pitx1 but not Tbx4 |
complete | ||||
| GO:0035116: embryonic hindlimb morphogenesis |
ECO:0000315: |
P |
Figure 4 (B) shows that when Pitx1 is knocked out, peroneus longus muscle and tendon are absent. Discussion in article notes these findings are due to improper skeletal structure development. In addition, it is inferred from discussion that the entire hindlimb is affected. |
complete | ||||
|
involved_in |
GO:0035116: embryonic hindlimb morphogenesis |
ECO:0000315: mutant phenotype evidence used in manual assertion |
P |
Seeded From UniProt |
complete | |||
Notes
See also
References
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