Is it possible tu induct the formation of medulloblastome in vermis or periventricular zone in cerebellum in rodent? if not in cerebellum .... in other area in central nervous system?
Aspm sustains postnatal cerebellar neurogenesis and medulloblastoma growth in mice.
Williams SE1, Garcia I2, Crowther AJ3, Li S2, Stewart A2, Liu H2, Lough KJ4, O'Neill S2, Veleta K3, Oyarzabal EA3, Merrill JR5, Shih YY6, Gershon TR7.
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Abstract
Alterations in genes that regulate brain size may contribute to both microcephaly and brain tumor formation. Here, we report that Aspm, a gene that is mutated in familial microcephaly, regulates postnatal neurogenesis in the cerebellum and supports the growth of medulloblastoma, the most common malignant pediatric brain tumor. Cerebellar granule neuron progenitors (CGNPs) express Aspm when maintained in a proliferative state by sonic hedgehog (Shh) signaling, and Aspm is expressed in Shh-driven medulloblastoma in mice. Genetic deletion of Aspm reduces cerebellar growth, while paradoxically increasing the mitotic rate of CGNPs. Aspm-deficient CGNPs show impaired mitotic progression, altered patterns of division orientation and differentiation, and increased DNA damage, which causes progenitor attrition through apoptosis. Deletion of Aspm in mice with Smo-induced medulloblastoma reduces tumor growth and increases DNA damage. Co-deletion of Aspm and either of the apoptosis regulators Bax or Trp53 (also known as p53) rescues the survival of neural progenitors and reduces the growth restriction imposed by Aspm deletion. Our data show that Aspm functions to regulate mitosis and to mitigate DNA damage during CGNP cell division, causes microcephaly through progenitor apoptosis when mutated, and sustains tumor growth in medulloblastoma.
https://www.ncbi.nlm.nih.gov/pubmed/26450969
Thank you so much Dr. Aldallal,
for sure this paper contain very useful information,
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