Impairment of <i>Sox9</i> Expression in Limb Buds of Rats Homozygous for Hypodactyly Mutation

Liška, František; Šnajdr, P.; Stricker, S.; Gosele, C.; Křenová, D.; Mundlos, S.; Hubner, N.

doi:10.14712/fb2010056020058

Folia Biologica > Archive > 2010, Vol. 56 > Issue 2 > Impairment of Sox9 Expression in…

Fol. Biol. 2010, 56, 58-65

https://doi.org/10.14712/fb2010056020058

Impairment of Sox9 Expression in Limb Buds of Rats Homozygous for Hypodactyly Mutation

František Liška¹, P. Šnajdr², S. Stricker³, C. Gosele⁴, D. Křenová¹, S. Mundlos³, N. Hubner⁴

¹Charles University in Prague, First Faculty of Medicine, Institute of Biology and Medical Genetics, Prague, Czech Republic
²Charles University in Prague, First Faculty of Medicine, Institute of Anatomy, Prague, Czech Republic
³Max-Planck-Institute for Molecular Genetics, Berlin, Germany
⁴Max-Delbrück-Center for Molecular Medicine (MDC), Berlin, Germany

Received June 2009
Accepted June 2009

Rat hypodactyly (hd) is an autosomal recessive mutation manifesting in homozygotes as reduction or loss of digits II and III. We mapped the hd allele to a short segment of chromosome 10, containing 16 genes. None of these genes has been shown to influence limb development yet. In situ hybridization showed no changes in several important patterning genes (Shh, Fgf8, Bmp2, 4, 7). However, we found that expression of cartilage condensation marker Sox9, and Bmp receptor Bmpr1b (acting as an upstream activator of Sox9 expression) is absent from the subepithelial mesenchyme of the digit condensations II and III. The failure of the chondrogenic condensations to extend towards the subepithelial mesenchyme may reduce the size of digit primordia and underlie the subsequent loss of phalanges and reduction of metacarpals/metatarsals in hd rats.

Keywords

limb development, hypodactyly, Sox9, Bmp signaling, the Norway rat.

Funding

This work was partially supported by the Czech Science Foundation (301/07/P178 to F.L., 304/06/0116 to D.K.) and by the Ministry of Education, Youth and Sports of the Czech Republic (MSMT CR 0021620806 to P.Š.)