of the Max - MDC

Structure of the Group
Group Leader
Prof. Dr. Carmen Birchmeier-
Kohler
Senior Scientists
Dr. Thomas Müller
Scientists
Dr. Hagen Wende
Dr. Nikolaus Karoulias
Dr. Robert Storm
Dr. Michael Strehle
Dr. Elena Vasyutina
Graduate and
Undergraduate Students
Mathias Gierl
Hendrik Wildner
Dominique Bröhl
Dinko Blazevizc
Jochen Welcker
Diana Lenhard
Justyna Cholewa-Waclaw
Kira Balueva
Technical Assistants
Karin Gottschling
Andrea Leschke
Sven Buchert
Animal Care
Petra Krause
Claudia Päseler
Secretariat
Sylvia Olbrich
Figure 3. Satellite cells are not generated in RBP-J mutant mice.
Satellite cells, the stem cells of the adult muscle, in control and
RBP-J mutant mice were identified by Pax7 expression. In control
animals, Pax7+ satellite cells (shown in red) are positioned under
the basal lamina, which outlines muscle fibers (laminin, green). In
RBP-J mutants, the population of satellite cells is not present.
Figure 4. Insm1 controls the differentiation of pancreatic beta-cells. Insulin expression
in the pancreas of Insm1 mutant mice at E18.5. (A, B) Immunohistological analysis
of Insm1 lacZ/+ and Insm1 lacZ/lacZ mice using antibodies directed against beta-galactosidase
(red) and insulin (green). (C) Proportion of the beta-galactosidase-positive cells that
express insulin. Double asterisks indicate p-values of < 0.001. Scale bar: 20µm.
Notch genes encode cell surface proteins, which are evolutionary
conserved and found in invertebrates like
Drosophila melanogaster as well as in all vertebrate species.
The transcription factor RBP-J (Rbpsuh) is the primary
nuclear mediator of Notch signals. We analyzed the function
of the Notch signaling system in myogenesis by conditional
mutagenesis of RBP-J. We found that the transcription factor
RBP-J, is essential to maintain this pool of muscle progenitor
cells in an undifferentiated state. In the absence of
RBP-J, these cells undergo uncontrolled myogenic differentiation,
leading to a depletion of the progenitor pool. This
results in reduced muscle growth in development and severe
muscle hypotrophy. In addition, satellite cells are not
formed in late fetal development in conditional RBP-J
mutant mice. We conclude that RBP-J is required in the
developing muscle to set aside proliferating progenitors and
satellite cells.
Selected Publications
Sieber MA, Storm R, Martinez-de-la-Torre M, Muller T, Wende H,
Reuter K, Vasyutina E, Birchmeier C. Lbx1 acts as a selector gene
in the fate determination of somatosensory and viscerosensory
relay neurons in the hindbrain. J Neurosci. 2007 May
2;27(18):4902-9.
Vasyutina E, Lenhard DC, Wende H, Erdmann B, Epstein JA,
Birchmeier C. RBP-J (Rbpsuh) is essential to maintain muscle
progenitor cells and to generate satellite cells. Proc Natl Acad Sci
U S A. 2007 Mar 13;104(11):4443-8.
Willem M, Garratt AN, Novak B, Citron M, Kaufmann S, Rittger A,
DeStrooper B, Saftig P, Birchmeier C, Haass C. Control of peripheral
nerve myelination by the beta-secretase BACE1. Science.
2006 Oct 27;314(5799):664-6.
Gierl MS, Karoulias N, Wende H, Strehle M, Birchmeier C. The
zinc-finger factor Insm1 (IA-1) is essential for the development
of pancreatic beta cells and intestinal endocrine cells. Genes
Dev. 2006 Sep 1;20(17):2465-78.
Wildner H, Muller T, Cho SH, Brohl D, Cepko CL, Guillemot F,
Birchmeier C. dILA neurons in the dorsal spinal cord are the product
of terminal and non-terminal asymmetric progenitor cell
divisions, and require Mash1 for their development.
Development. 2006 Jun;133(11):2105-13.
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