EXPRESSION PROFILE OF GLI FAMILY MEMBERS AND SHH IN NORMAL AND MUTANTMOUSE LIMB DEVELOPMENT

Gli genes represent a small family, encoding zinc-finger proteins of t he Kruppel-type, The family consists of Gli(1), Gli2, and Gli3, all of which are expressed in the developing mouse limb bud. To assess the r ole of the Gli family and Sonic hedgehog (Shh) in mouse limb developme nt, we compared the expression domains of all three Gli genes and of S hh. Although each Gli gene has its own distinct expression pattern in limb buds, at 10.5-11.5 dpc all three genes were found not to be expre ssed in the posterior region, the presumptive Shh expression domain. T his transient mutually exclusive expression suggested a potential inte raction between Gli genes and Shh. To address this matter, we analysed the expression of Gli genes and Shh in two polydactyly mouse mutants, Extra foes (Xt) and Hemimelic-extra toes (Hx) which express Shh ectop ically in the anterior region of the limb held. Since Xt mice lack Gli 3 expression, the ectopic Shh expression is genetically Linked to the absence of Gli3, In Hx mice we found a down-regulation of Gli3 in the anterior region of the limb bud, In both mutants Gli2 expression patte rn was not altered, whereas Gli1 expression was anteriorly up-regulate d adjacent to the ectopic Shh domain, These results strongly suggest a positive regulation of Gli1 by Shh and a negative interaction between Shh and Gli3. (C) 1998 Wiley-Liss, Inc.