Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0153640 (Cerebellum)
 1,777 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

LIN28B is a homologue of the RNA-binding protein LIN28A and regulates gene expression during development and carcinogenesis. It is strongly upregulated in a variety of brain tumors, such as medulloblastoma, embryonal tumor with multilayered rosettes (ETMR), atypical teratoid/rhabdoid tumor (AT/RT), or glioblastoma, but the effect of an in vivo overexpression of LIN28B on the developing central nervous system is unknown. We generated transgenic mice that either overexpressed Lin28b in Math1-positive cerebellar granule neuron precursors or in a broad range of Nestin-positive neural precursors. Sections of the cerebellar vermis from adult Math1-Cre::lsl-Lin28b mice had an additional subfissure in lobule IV. Vermes from p0 and p7 Nestin-Cre::lsl-Lin28b mice appeared normal, but we found a pronounced vermal hypersublobulation at p15 and p21 in these mice. Also, the external granule cell layer (EGL) was thicker at p15 than in controls, contained more proliferating cells, and persisted up to p21. Consistently, some Pax6- and NeuN-positive cells were present in the EGL of Nestin-Cre::lsl-Lin28b mice even at p21, and we detected more NeuN-positive granule neuron precursors in the molecular layer (ML) as compared to control. Finally, we found some residual Pax2-positive precursors of inhibitory interneurons in the ML of Nestin-Cre::lsl-Lin28b mice at p21, which have already disappeared in controls. We conclude that while overexpression of LIN28B in Nestin-positive cells does not lead to tumor formation, it results in a protracted development of granule cells and inhibitory interneurons and leads to a hypersublobulation of the cerebellar vermis.
Cerebellum 2017 02
PMID:Overexpression of Lin28b in Neural Stem Cells is Insufficient for Brain Tumor Formation, but Induces Pathological Lobulation of the Developing Cerebellum. 2703 94

In the developing cerebellum, the nascent white matter (WM) serves as an instructive niche for cerebellar cortical inhibitory interneurons. As their Pax2 expressing precursors transit the emerging WM, their laminar fate is programmed. The source(s) and nature of the signals involved remain unknown. Here, we used immunocytochemistry to follow the cellular maturation of the murine cerebellar WM during this critical period. During the first few days of postnatal development, when most Pax2 expressing cells are formed and many of them reach the cerebellar gray matter, only microglial cells can be identified in the territories through which Pax2 cells migrate. From p4 onward, cells expressing the oligodendrocytic or astrocyte markers, CNP-1, MBP or GFAP, started to appear in the nascent WM. Expression of macroglial markers increased with cerebellar differentiation, yet deep nuclei remained GFAP-negative at all ages. The progressive spread of maturing glia did not correlate with the exit of Pax2 cells from the WM, as indicated by the extensive mingling of these cells up to p15. Whereas sonic hedgehog-associated p75NTR expression could be verified in granule cell precursors, postmitotic Pax2 cells are p75NTR negative at all ages analyzed. Thus, if Pax2 cells, like their precursors, are sensitive to sonic hedgehog, this does not affect their expression of p75NTR. Our findings document that subsequently generated sets of Pax2 expressing precursors of inhibitory cerebellar interneurons are confronted with a dynamically changing complement of cerebellar glia. The eventual identification of fate-defining pathways should profit from the covariation with glial maturation predicted by the present findings.
Cerebellum 2020 Apr
PMID:Developmental Maturation of the Cerebellar White Matter-an Instructive Environment for Cerebellar Inhibitory Interneurons. 3200 2