of the Max - MDC
of the Max - MDC
of the Max - MDC
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Structure <strong>of</strong> <strong>the</strong> Group<br />
Group Leader<br />
Dr. Annette Hammes<br />
Graduate Students<br />
Chandresh Gajera*<br />
Annabel Christ<br />
* part <strong>of</strong> <strong>the</strong> period reported<br />
Adult neurogenesis: a role <strong>of</strong> megalin in <strong>the</strong><br />
adult brain<br />
(collaboration with Gerd Kempermann and Thomas<br />
Willnow)<br />
An additional aim is to define <strong>the</strong> role <strong>of</strong> megalin in adult<br />
neurogenesis.<br />
In <strong>the</strong> adult brain, megalin is expressed in ependymal cells,<br />
an epi<strong>the</strong>lial layer covering <strong>the</strong> brain ventricles. Intriguingly,<br />
we found strongest expression in <strong>the</strong> ependyma <strong>of</strong> <strong>the</strong> lateral<br />
wall <strong>of</strong> <strong>the</strong> lateral ventricles. This cell layer plays a crucial<br />
role in controlling <strong>the</strong> generation <strong>of</strong> adult neurons from neuronal<br />
precursor cells in <strong>the</strong> subventricular zone (SVZ) <strong>of</strong> <strong>the</strong><br />
lateral ventricles.<br />
Megalin-deficiency does not grossly affect <strong>the</strong> composition<br />
<strong>of</strong> <strong>the</strong> SVZ in adult mouse mutants but we observed decreased<br />
cell proliferation in <strong>the</strong> lateral wall <strong>of</strong> <strong>the</strong> lateral ventricle<br />
and phenotypic changes in SVZ neuronal precursor cells.<br />
Interestingly, SHH stimulates adult neurogenesis in <strong>the</strong> SVZ,<br />
and this effect requires repression <strong>of</strong> BMP activity via chordin<br />
and noggin. The role <strong>of</strong> megalin in regulation <strong>of</strong> neurogenesis<br />
via SHH and BMP signalling pathways during development<br />
strongly indicates a link between mechanisms in <strong>the</strong> embryo<br />
and in <strong>the</strong> adult. Thus megalin might modulate levels <strong>of</strong> <strong>the</strong><br />
neurogenesis-inhibiting factor BMP4. We will address <strong>the</strong><br />
potential role <strong>of</strong> megalin in adult neurogenesis by fur<strong>the</strong>r<br />
detailed analyses <strong>of</strong> <strong>the</strong> adult megalin -/- mice.<br />
The potential role <strong>of</strong> megalin in adult neurogenesis may have<br />
far reaching implications for <strong>the</strong> development <strong>of</strong> molecular<br />
approaches to support adult neurogenesis in <strong>the</strong> aging brain<br />
and in neurodegenerative diseases.<br />
Selected Publications<br />
Willnow, TE, Hammes, A, Eaton, S. (2007) Lipoproteins and <strong>the</strong>ir<br />
receptors in embryonic development – more than cholesterol<br />
clearance. Development, in press<br />
Hammes, A, Andreassen, TK, Spoelgen, R, Raila, J, Hubner, N,<br />
Schulz, H, Metzger, J, Schweigert, FJ, Luppa, PB, Nykjaer, A,<br />
Willnow, TE. (2005) Role <strong>of</strong> endocytosis in cellular uptake <strong>of</strong> sex<br />
steroids. Cell 122(5): 751-762.<br />
Spoelgen, R, Hammes, A, Anzenberger, U, Zechner, D, Andersen,<br />
OM, Jerchow, B, Willnow, TE. (2005) LRP2/megalin is required<br />
for patterning <strong>of</strong> <strong>the</strong> ventral telencephalon. Development<br />
132(2): 405-414.<br />
10 Cardiovascular and Metabolic Disease Research
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