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Presenting Author(s) Atsushi Kuroiwa
Abstract Title Tissue interaction and Hox genes control Six2 expression in the tendon precursor cells.
Full author List Atsushi Kuroiwa and Yo-ichi Shiraishi
Text of abstract It is well known that pattering of the limb connective tissue in under the control of the tissue interaction between limb mesenchyme and cartilage/muscle. We analyzed the mechanism for tendon differentiation from the limb mesenchyme in the autopod using Six2 as a marker. Six2 expression in the autopod was first detected in the mesenchyme overlaying the carpal/tarsal cartilage, then the expression expanded distally in the mesenchyme overlaying metacarpal/metatarsal and digital cartilage as stripes following their development. Removal of the surface ectoderm inhibited Six2 expression and transplantation of the cartilage induced Six2 expression. Wnt genes are expressed in the limb ectoderm and known to repress cartilage differentiation. We found misexpression of Wnt3a in the limb mesenchyme induced extopic Six2 expression. Local administration of BMP2 repress Six2 expression and BMP antagonist noggin allowed expansion of Six2 expression domain. Since noggin is reported to be expressed in the cartilage reached to certain stage of differentiation, noggin is a candidate of the cartilage factor for Six2 induction. Six2 expression in the autopod is found in the region where two signals meet it is possible that combination of Wnt from the ectoderm and BMP antagonist from the cartilage is required for Six2 expression. These two signals seems to be separated by muscle mass in the zeugopod. We interfered muscle invasion to the limb bud and found that no change in Six2 expression took place. It is possible that the sensitivity of the mesenchyme to these signals is different between autopod and zeugopod. We examined the contribution of Hox genes that specify positional identity for cartilage pattern formation. Misexpression of Hoxa-13 in the zeugopod induced ectopic expansion of Six2 expression domain at carpal/tarsal region toward the zeugopod. Taking account these finding, Hox genes and signals from adjacent tissue regulate Six2 expression in a concerted manner.
Which session is your work most relevant to: Tissue differentiation