(Left) In healthy mice a stem cell (red) resides in a special niche
between the muscle cell and the basal lamina (green) which surrounds it.
(Right) If the Notch signaling pathway is mutated, the stem cell locates
outside of the muscle fiber and hardly contributes to muscle growth.
Photo: Dr. Dominique Bröhl/ Copyright: MDC
Muscle Stem Cells Must Be In The Right Place at The Right Time
Muscle stem cells must reside within special niches inside muscle fibers for efficient growth and repair of muscle tissue
Muscles have a pool of stem cells which provide for growth and regeneration of muscle cells when injured. However, they must reside within special niches in the muscle fiber to work.
Developmental biologists Dr. Dominique Bröhl and Prof. Carmen Birchmeier of the Max Delbrück Center for Molecular Medicine (MDC) Berlin-Buch have discovered how these stem cells colonize their niches. At the same time, the scientists show that the stem cells weaken the muscle overall when, due to a mutation, they locate outside of the muscle fibers instead.
Their work was published August 30, 2012, in the journal Developmental Cell.
Muscle stem cells, also called satellite cells,
colonize a niche that is located between the
plasma membrane of the muscle cell and
the surrounding basal lamina.
Already in newborns, these niches contain
satellite cells which generate both
muscle cells and new stem cells.
Weakened Stem Cells
In their study, Dr. Bröhl and Professor Birchmeier show that mouse muscle satellite and progenitor cells lacking components from the Notch signaling pathway, cannot colonize niches.
Instead the mutated cells lodge between the muscle fibers. The biologists believe this is what causes weakening of the muscles as the stem cells that are “in the wrong place” no longer potent contribute to myofiber growth.
From the Abstract:
Elimination of Notch signals during mouse development
results in premature differentiation of myogenic
progenitors and formation of very small muscle groups.
Here we show that this drastic effect is rescued by
mutation of the muscle differentiation factor MyoD.
However, rescued myogenic progenitors do not assume
a satellite cell position and contribute poorly to myofiber
growth. The disrupted homing is due to a deficit
in basal lamina assembly around emerging satellite cells
and to their impaired adhesion to myofibers.
We conclude that Notch signals control homing
of satellite cells, stimulating them to contribute
to their own microenvironment and
to adhere to myofibers.
Developmental Cell, Volume 23, Issue 3, 469-481, 30 August 2012
The Notch signaling pathway has a second function in muscle development. It prevents differentiation of stem cells into muscle cells by suppressing the muscle developmental factor MyoD thus ensuring there will always be a pool of stem cells for muscle repair and regeneration.
In the future this work could gain in importance for research on muscle regeneration and muscle weakness.
*Colonization of the Satellite Cell Niche by Skeletal Muscle Progenitor Cells Depends on Notch Signals
Dominique Bröhl1, Elena Vasyutina1,#, Maciej T. Czajkowski1, Joscha Griger1, Claudia Rassek1, Hans-Peter Rahn2, Bettina Purfürst3, Hagen Wende1 and Carmen Birchmeier1*
1Developmental Biology/Signal Transduction Group, 2Preparative Flow Cytometry and 3Electron Microscopy Core Facility
Max-Delbrück-Center for Molecular Medicine, Robert-Rössle-Str. 10, 13125 Berlin, Germany
#Present address: Department of Medicine 1, University of Cologne, Kerpener Str. 62, 50924 Cologne, Germany
Max Delbrück Center for Molecular Medicine (MDC) Berlin-Buch
in the Helmholtz Association
Robert-Rössle-Straße 10; 13125 Berlin, Germany
Original article: http://www.mdc-berlin.de/en/news/2012/20120917-at_the_right_place_at_the_right_time/index.html