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Loss of the Tg737 protein results in skeletal patterning defects
Author(s) -
Zhang Qihong,
Murcia Noel S.,
Chittenden Laura R.,
Richards William G.,
Michaud Edward J.,
Woychik Richard P.,
Yoder Bradley K.
Publication year - 2003
Publication title -
developmental dynamics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.634
H-Index - 141
eISSN - 1097-0177
pISSN - 1058-8388
DOI - 10.1002/dvdy.10289
Subject(s) - biology , mesenchyme , apical ectodermal ridge , limb development , phenotype , polydactyly , allele , embryonic stem cell , mutant , transgene , microbiology and biotechnology , null allele , limb bud , genetics , anatomy , embryo , mesoderm , gene
Tg737 mutant mice exhibit pathologic conditions in numerous tissues along with skeletal patterning defects. Herein, we characterize the skeletal pathologic conditions and confirm a role for Tg737 in skeletal patterning through transgenic rescue. Analyses were conducted in both the hypomorphic Tg737 orpk allele that results in duplication of digit one and in the null Tg737 Δ2‐3βGal allele that is an embryonic lethal mutation exhibiting eight digits per limb. In early limb buds, Tg737 expression is detected throughout the mesenchyme becoming concentrated in precartilage condensations at later stages. In situ analyses indicate that the Tg737 orpk mutant limb defects are not associated with changes in expression of Shh , Ihh , HoxD11–13 , Patched , BMPs , or Glis . Likewise, in Tg737 Δ2‐3βGal mutant embryos, there was no change in Shh expression. However, in both alleles, Fgf4 was ectopically expressed on the anterior apical ectodermal ridge. Collectively, the data argue for a dosage effect of Tg737 on the limb phenotypes and that the polydactyly is independent of Shh misexpression. Developmental Dynamics 227:78–90, 2003. © 2003 Wiley‐Liss, Inc.