Abstracts (complete list) - Wissenschaft Online

Kai Dittmann, Anja Uhmann, Ralf Dressel, Heidi Hahn, Jürgen Wienands
Targeted inactivation of the Hh receptor Ptch abrogates
lymphocyte development in mice
The Hh/Ptch signaling system is known to control the development and neoplastic
transformation of several cell types. However, the role of Hh/Ptch for the differentiation
of B and T lymphocytes from hematopoietic stem cells (HSC) has not been assessed so
far. To analyze the function of Hh/Ptch for lymphopoiesis in vivo, we have employed a
genetically engineered mouse mutant in which the Ptch gene can be conditionally
inactivated by virtue of the Cre/loxP recombination system. We show that targeted
disruption of Ptch in the adult organism results in a dramatic specification and
differentiation defect of the lymphoid lineage leading to rapid disappearance of newly
generated B and T lymphocytes from peripheral lymphoid organs. The developmental
block occurs at the level of the common lymphoid progenitor cell (CLP), which defines
an early branching point of HSC differentiation and lineage commitment. In contrast to
the lymphoid lineage, development of cell types of the myeloid lineage from common
myeloid progenitors (CMP) appears normal. Our data identify Hh/Ptch-induced signaling
as a key regulator for proper development of immunocompetent lymphocytes. Hence,
the progression of tumors, which are initiated upon oncogenic Hh/Ptch mutations, may
be further promoted due to impaired tumor surveillance by a compromised immune
system.