03-P019 Sip1 has an essential role during hair follicle induction

Sip1 is a member of the family of two-handed zinc finger/ homeodomain proteins identified as a DNA binding transcriptional repressor interacting with receptor-activated SMADs. SMADs are intracellular signal transducers activated by binding of TGFb/BMP ligands to their receptors and are involved in the control of cellular functions of embryonic development and tissue homeostasis. During mouse and chick limb development, the Sip1 mRNA expression was detected in the developing limb in a cell population with unknown function. Since the general inactivation of Sip1 gene resulted in early embryonic lethality, we decided to investigate the function of Sip1 during limb development using a conditional gene inactivation. We have used available Sip1 floxed allele to inactivate Sip1 in developing limbs using Prx1-Cre mouse. In these mice, Cre is expressed in the limb mesenchyme from the early developmental stages (10 dpc) onwards as well as in the parts of developing brain. Prx1-Cre; Sip1 mice are viable but phenotypically, the mice have no hair on the developing limbs and part of the head. Histologically there is a significant reduction in the number of hair follicles and the remaining hair follicles had abnormally small dermal condensates. There were significant changes in the expression levels of marker genes associated with early induction of hair follicles such as members of Wnt and BMP families of ligands and their target genes. The present results point out the essential role of SIP1 in the induction of hair follicles and suggest a novel function for SIP1during hair follicle morphogenesis.