title: Misexpression of Pknox2 in mouse limb bud mesenchyme perturbs zeugopod development and deltoid crest formation.
abstract: The TALE (Three Amino acid Loop Extension) family consisting of Meis, Pbx and Pknox proteins is a group of transcriptional co-factors with atypical homeodomains that play pivotal roles in limb development. Compared to the in-depth investigations of Meis and Pbx protein functions, the role of Pknox2 in limb development remains unclear. Here, we showed that Pknox2 was mainly expressed in the zeugopod domain of the murine limb at E10.5 and E11.5. Misexpression of Pknox2 in the limb bud mesenchyme of transgenic mice led to deformities in the zeugopod and forelimb stylopod deltoid crest, but left the autopod and other stylopod skeletons largely intact. These malformations in zeugopod skeletons were recapitulated in mice overexpressing Pknox2 in osteochondroprogenitor cells. Molecular and cellular analyses indicated that the misexpression of Pknox2 in limb bud mesenchyme perturbed the Hox10-11 gene expression profiles, decreased Col2 expression and Bmp/Smad signaling activity in the limb. These results indicated that Pknox2 misexpression affected mesenchymal condensation and early chondrogenic differentiation in the zeugopod skeletons of transgenic embryos, suggesting Pknox2 as a potential regulator of zeugopod and deltoid crest formation.
authors.affiliation: Bio-X Institutes, Key Laboratory for the Genetics of Developmental and Neuropsychiatric Disorders-Ministry of Education, Shanghai Jiao Tong University, Shanghai, China.
authors.forename: Wenrong
authors.initials: W
authors.lastname: Zhou
authors.forename: Huang
authors.initials: H
authors.lastname: Zhu
authors.forename: Jianzhi
authors.initials: J
authors.lastname: Zhao
authors.forename: Hanjun
authors.initials: H
authors.lastname: Li
authors.forename: Yong
authors.initials: Y
authors.lastname: Wan
authors.forename: Jingjing
authors.initials: J
authors.lastname: Cao
authors.forename: Haixia
authors.initials: H
authors.lastname: Zhao
authors.forename: Jian
authors.initials: J
authors.lastname: Yu
authors.forename: Rujiang
authors.initials: R
authors.lastname: Zhou
authors.forename: Yiyun
authors.initials: Y
authors.lastname: Yao
authors.forename: Lingling
authors.initials: L
authors.lastname: Zhang
authors.forename: Lifang
authors.initials: L
authors.lastname: Wang
authors.forename: Lin
authors.initials: L
authors.lastname: He
authors.forename: Gang
authors.initials: G
authors.lastname: Ma
authors.forename: Zhengju
authors.initials: Z
authors.lastname: Yao
authors.forename: Xizhi
authors.initials: X
authors.lastname: Guo
mesh_terms: D000818:Animals; D001483:Base Sequence; D019902:Chondrocytes / Q000378:metabolism; D017931:DNA Primers; D018398:Homeodomain Proteins / Q000235:genetics*; D018878:Limb Buds / Q000196:embryology* / Q000502:physiology; D008648:Mesoderm; D051379:Mice; D008822:Mice, Transgenic; D010006:Osteoblasts / Q000378:metabolism; D013234:Stem Cells / Q000378:metabolism; D014157:Transcription Factors / Q000235:genetics*
chemical_list: D017931:DNA Primers; D018398:Homeodomain Proteins; C486665:Pknox2 protein, mouse; D014157:Transcription Factors