Indian Hedgehog Is Essential for Definitive Haematopoiesis in the Fetal Liver.

Indian hedgehog (Ihh) is a member of the hedgehog family of secreted proteins which play diverse roles in development. Members of this family have established roles in craniofacial development, long bone formation and spermatogenesis. Mammals have three hedgehog proteins which all act through the Patched receptor to activate smoothened and downstream zinc finger transcription factors of the Gli family. Ihh can induce differentiation of primitive red blood cells during primitive streak formation, and definitive red blood cells from CD34+ cord blood stem cells. Both Ihh and the Patched receptor are expressed in the fetal liver. In this report we show Ihh knockout mice display a partially penetrant defect in fetal liver haematopoiesis characterised by severe anaemia and apoptosis of the fetal liver erythroid compartment. Primitive haematopoiesis is normal, so mutant embryos survive until ∼E14. Components of the hedgehog signalling pathway are expressed in stromal, stem cell and progenitor cell components of the haematopoietic system. Lastly, fetal liver progenitor cells (CFU-e, BFU-e, and myeloid CFUs) are normal in Ihh null mice, suggesting a critical requirement for Ihh in the fetal liver stem cell niche.