Research Report 2000 - MDC

Lbx1, c-met and the control of
cell migration of muscle
precursor cells
H. Brohmann
Muscle of the extremities is generated
by migrating myogenic precursor
cells. These precursors delaminate
from the lateral edge of the
dermomyotome and form distinct
streams that migrate over large
distances, using characteristic paths.
We are characterising the genetic
hierarchy that controls the migration
of this lineage. We have previously
shown that the c-met tyrosine kinase
receptor and its ligand, SF/HGF, are
essential for the delamination of cells.
Moreover, SF/HGF is expressed along
the entire migratory route of muscle
precursor cells, indicating that this
signaling system plays a role also
during the migration process. Indeed,
we are currently analysing mice with
reduced c-met signaling capacity,
which show abnormal limb muscle
development and abnormal migration
of precursor cells. The homeobox
gene Lbx1 is expressed in migrating,
but not in other types of muscle
precursor cells. We have used gene
targeting to analyse the function of
Lbx1 in the mouse. Myogenic
precursor cells delaminate from the
dermomyotome in Lbx1 mutants, but
migrate in an aberrant manner, and do
not reach the dorsal limb field. In the
ventral limb, precursors are present
but distributed abnormally. As a
consequence, at birth some muscles in
the forelimbs are completely lacking
(extensor muscles) or reduced in size
(flexor muscles).
Selected Publications
Gaio, U. Schweickert, A., Fischer, A.
Garratt, A. N., Müller, T., Özcelik, C.,
Lankes, W., Strehle, M., Britsch, S.,
Blum, M., and Birchmeier, C. (1999)
A role of the cryptic gene in the
correct establishment of the left-right
axis. Current Biology 9, 1339-1342.
Woldeyesus, M.T., Britsch, S.,
Riethmacher, D. Xu, L., Sonnenberg-
Riethmacher, E., Harvey, R., Caroni,
P., and Birchmeier, C. (1999) Genetic
rescue of cardiac morphogenesis in
erbB2 mutant mice reveals functions
of the ErbB2 receptor in development
of the peripheral nervous system.
Genes & Dev. 19, 2538-2548.
Dietrich, S., Abou-Rebyeh, F.,
Brohmann, H., Bladt, F., Sonnenberg-
Riethmacher, E., Yamaai, T.,
Lumsden, A., Brand-Saberi, B., and
Birchmeier C. (1999) The role of
SF/HGF and c-Met in the
development of skeletal muscle.
Development 126, 1621-1629.
Birchmeier, C., and Gherardi, E.
(1998) Developmental functions of
scatter factor/hepatocyte growth factor
(SF/HGF) and its receptor, the c-met
tyrosine kinase. Trends Cell Biol. 8,
404-410.
Britsch, S., Li, L., Kirchhoff, S.,
Theuring, F., Brinkmann, V.,
Birchmeier, C., and Riethmacher, D.
(1998) The ErbB2 and ErbB3
receptors and their ligand, neuregulin-
1, are essential for development of the
sympathetic nervous system. Genes &
Dev. 12, 1825-1836.
Structure of the Group
Group leader
Dr. Carmen Birchmeier
Scientists
Dr. Stefan Britsch
Dr. Alistair Garratt
Dr. Thomas Müller
Dieter Riethmacher*
Eva Sonnenberg-Riethmacher*
Dr. Cemil Öczelik*
Dr. Wolfgang Lankes*
Graduate and undergraduate students
Henning Brohmann
Ursula Gaio
Li Li
Martin Sieber*
Michael Strehle
Mas Woldeyesus
Technical assistants
Sven Buchert
Karin Gottschling
Cathrin Rudolph
Secretariat
Brigitta Wedekind
*part of the period reported
Figure 19: Aberrant migration of myogenic
precursor cells in Lbx1 mutant embryos.
Myogenic precursor cells in control (A), and
Lbx1-/- (B) embryos at E9.75 were visualized
by in situ hybridization using a Pax3 specific
probe. Myogenic precursor cells detach from
the dermomyotome in Lbx1 mutants, but do not
migrate appropriately to the limb bud. In
control embryos, the precursor cells have
reached the limb bud at this stage.
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