Ectopic Meis1 expression in the mouse limb bud alters P-D patterning in a Pbx1-independent manner. Mercader, N., Selleri, L., Criado, L., M., Pallares, P., Parras, C., Cleary, M., L., & Torres, M. The International journal of developmental biology, 53(8-10):1483-94, 1, 2009. Paper Website abstract bibtex 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.
@article{
title = {Ectopic Meis1 expression in the mouse limb bud alters P-D patterning in a Pbx1-independent manner.},
type = {article},
year = {2009},
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keywords = {Animals,Body Patterning,Body Patterning: genetics,Body Patterning: physiology,Embryo, Mammalian,Embryo, Mammalian: embryology,Embryo, Mammalian: metabolism,Gene Expression Regulation, Developmental,Homeodomain Proteins,Homeodomain Proteins: genetics,Homeodomain Proteins: metabolism,Homeodomain Proteins: physiology,Immunohistochemistry,In Situ Hybridization,Limb Buds,Limb Buds: embryology,Limb Buds: metabolism,Mice,Mice, Inbred C57BL,Mice, Transgenic,Neoplasm Proteins,Neoplasm Proteins: genetics,Neoplasm Proteins: metabolism,Neoplasm Proteins: physiology,Time Factors,Transcription Factors,Transcription Factors: genetics,Transcription Factors: metabolism,Transcription Factors: physiology},
pages = {1483-94},
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abstract = {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.},
bibtype = {article},
author = {Mercader, Nadia and Selleri, Licia and Criado, Luis Miguel and Pallares, Pilar and Parras, Carlos and Cleary, Michael L and Torres, Miguel},
journal = {The International journal of developmental biology},
number = {8-10}
}
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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.","bibtype":"article","author":"Mercader, Nadia and Selleri, Licia and Criado, Luis Miguel and Pallares, Pilar and Parras, Carlos and Cleary, Michael L and Torres, Miguel","journal":"The International journal of developmental biology","number":"8-10","bibtex":"@article{\n title = {Ectopic Meis1 expression in the mouse limb bud alters P-D patterning in a Pbx1-independent manner.},\n type = {article},\n year = {2009},\n identifiers = {[object Object]},\n keywords = {Animals,Body Patterning,Body Patterning: genetics,Body Patterning: physiology,Embryo, Mammalian,Embryo, Mammalian: embryology,Embryo, Mammalian: metabolism,Gene Expression Regulation, Developmental,Homeodomain Proteins,Homeodomain Proteins: genetics,Homeodomain Proteins: metabolism,Homeodomain Proteins: physiology,Immunohistochemistry,In Situ Hybridization,Limb Buds,Limb Buds: embryology,Limb Buds: metabolism,Mice,Mice, Inbred C57BL,Mice, Transgenic,Neoplasm Proteins,Neoplasm Proteins: genetics,Neoplasm Proteins: metabolism,Neoplasm Proteins: physiology,Time Factors,Transcription Factors,Transcription Factors: genetics,Transcription Factors: metabolism,Transcription Factors: physiology},\n pages = {1483-94},\n volume = {53},\n websites = {http://www.ncbi.nlm.nih.gov/pubmed/19247936},\n month = {1},\n id = {126d963a-2456-3fa6-94ca-b4f994d865d7},\n created = {2016-04-08T12:19:35.000Z},\n accessed = {2014-01-20},\n file_attached = {true},\n profile_id = {994bc413-6766-31df-917a-32165aa30f6c},\n group_id = {cec5aa9e-65e1-3c21-bc44-78fa6504020e},\n last_modified = {2017-03-14T10:42:46.538Z},\n read = {true},\n starred = {false},\n authored = {false},\n confirmed = {true},\n hidden = {false},\n citation_key = {Mercader2009},\n folder_uuids = {37786225-e8d4-483b-be04-dfc97f200748},\n private_publication = {false},\n abstract = {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. 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