of the Max - MDC

Function and Dysfunction of the Nervous System
Coordinators: Carmen Birchmeier-Kohler, Helmut Kettenmann
Signal Transduction/
Developmental Biology
Carmen Birchmeier
We analyze the functions of signaling molecules and of transcription factors in development of the nervous
system and muscle. For this work, we use mice as a model organism. The molecular genetics of mice is well
developed, and homologous recombination combined with embryonic stem cell technology can be used to introduce
deletions or insertions into the genome. A further development of the technique, the Cre/LoxP technology,
allows us now to introduce conditional mutations that are restricted to a particular cell lineage. We have used
these technologies to analyze signals that maintain muscle progenitor cells and that allow the formation of
satellite cells, the stem cells of the adult muscle. In addition, we identified the function of several transcription
factors in development of the nervous system. Among these is a novel factor, Insm1,that we found unexpectedly
to perform also important functions in development of pancreatic beta-cells, the insulin-producing endocrine
cells.
Development of the spinal cord and hindbrain
Thomas Müller, Robert Storm, Hendrik Wildner,
Dominique Bröhl
The adult nervous system is characterized by a multitude of
different neuron types that interact in complex neuronal
circuits. The distinct neuronal subtypes are generated in a
defined and invariant spatial and temporal order during
development, and the ordered generation of neurons is a
prerequisite for the establishment of the correct neuronal
connectivity. We have concentrated in the last years on the
characterization of neurons in the dorsal spinal cord and
hindbrain, which receive and process sensory information
from the periphery. These neurons are thus important for
sensory perceptions, for instance for the sensation of pain.
Lbx1 functions in neuronal development
Rober Storm, Thomas Müller
The hindbrain is the part of the central nervous system that
monitors and regulates inner organ function and thereby
controls heart beat, blood pressure and breathing. To
achieve this, hindbrain neurons receive and integrate sensory
information form inner organs (viscerosensory information).
The hindbrain also receives and processes sensory
information about touch and pain from the face
(somatosensory). Neurons that process viscerosensory and
somatosensory information cluster in different hindbrain
nuclei. How neurons choose between these two fates was
unclear. We found that the homeobox gene Lbx1 is essential
for imposing a somatosensory fate on relay neurons in the
hindbrain. In Lbx1 mutant mice, viscerosensory relay neurons
are generated at the expense of somatosensory relay
neurons. Thus, Lbx1 expression distinguishes between the
somatosensory and viscerosensory fates of relay neurons.
Lbx1 is expressed in the spinal cord and hindbrain, and our
analyses showed similarities in Lbx1 function in these two
units of the developing nervous system. Developing neurons
that will process somatosensory information in the spinal
cord and hindbrain are characterized by the expression of a
particular set of homeodomain transcription factors, among
them Lbx1. These neurons of the hindbrain and the spinal
cord exhibit functional similarities, and process somatosensory
information of the face and the body, respectively. In
Lbx1 mutant mice, somatosensory relay neurons are mis-
152 Function and Dysfunction of the Nervous System