Mercader Huber, Nadia; Selleri, Licia; Criado, Luis Miguel; Pallares, Pilar; Parras, Carlos; Cleary, Michael L; Torres, Miguel (2009). Ectopic Meis1 expression in the mouse limb bud alters P-D patterning in a Pbx1-independent manner. The International Journal of Developmental Biology, 53(8-10), pp. 1483-1494. UBC Press 10.1387/ijdb.072430nm
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During limb development, expression of the TALE homeobox transcription factor Meis1 is activated by retinoic acid in the proximal-most limb bud regions, which give rise to the upper forelimb and hindlimb. Early subdivision of the limb bud into proximal Meis-positive and distal Meis-negative domains is necessary for correct proximo-distal (P-D) limb development in the chick, since ectopic Meis1 overexpression abolishes distal limb structures, produces a proximal shift of limb identities along the P-D axis, and proximalizes distal limb cell affinity properties. To determine whether Meis activity is also required for P-D limb specification in mammals, we generated transgenic mice ectopically expressing Meis1 in the distal limb mesenchyme under the control of the Msx2 promoter. Msx2:Meis1 transgenic mice display altered P-D patterning and shifted P-D Hox gene expression domains, similar to those previously described for the chicken. Meis proteins function in cooperation with PBX factors, another TALE homeodomain subfamily. Meis-Pbx interaction is required for nuclear localization of both proteins in cell culture, and is important for their DNA-binding and transactivation efficiency. During limb development, Pbx1 nuclear expression correlates with the Meis expression domain, and Pbx1 has been proposed as the main Meis partner in this context; however, we found that Pbx1 deficiency did not modify the limb phenotype of Msx2:Meis1 mice. Our results indicate a conserved role of Meis activity in P-D specification of the tetrapod limb and suggest that Pbx function in this context is either not required or is provided by partners other than Pbx1.
Item Type: |
Journal Article (Original Article) |
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Division/Institute: |
04 Faculty of Medicine > Pre-clinic Human Medicine > Institute of Anatomy |
UniBE Contributor: |
Mercader Huber, Nadia Isabel |
Subjects: |
600 Technology > 610 Medicine & health |
ISSN: |
0214-6282 |
Publisher: |
UBC Press |
Language: |
English |
Submitter: |
Nadia Isabel Mercader Huber |
Date Deposited: |
30 Jun 2016 15:17 |
Last Modified: |
02 Mar 2023 23:27 |
Publisher DOI: |
10.1387/ijdb.072430nm |
PubMed ID: |
19247936 |
BORIS DOI: |
10.7892/boris.79624 |
URI: |
https://boris.unibe.ch/id/eprint/79624 |
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