Cerebellar 'transcriptome' reveals cell-type and stage-specific expression during postnatal development and tumorigenesis.
Disorders of cerebellar development can result in neurological disease and cancer. The identity of transcription factors that may uniquely mark and/or regulate development of single cerebellar cell types, however, is poorly understood. We used a library of approximately 1100 probes for expression of transcription factor (TF)-encoding genes (>70% of the mammalian 'transcriptome') to identify 227 genes with expression in developing neuronal and glial populations and 24 TFs that show cell-type- and stage-specific expression in granule cells, Purkinje cells and interneurons during postnatal cerebellar development. The utility of this panel is exemplified by analysis of medulloblastoma that shows upregulation of markers specific for early granule cell lineage, but not for other neuronal cell types, indicative of a unipotent precursor as well as a block in granule cell differentiation within the tumor. We propose that this atlas of the cerebellar transcriptome and the panel of 24 validated markers will be generally useful in analyses of mutations affecting postnatal cerebellar development and neoplasia.
Schüller
Ulrich
U
Department of Pediatric Oncology, Dana-Farber Cancer Institute, 44 Binney Street, Boston, MA 02115, USA.
Kho
Alvin T
AT
Zhao
Qing
Q
Ma
Qiufu
Q
Rowitch
David H
DH
D000818:Animals; D000831:Animals, Newborn; D002454:Cell Differentiation / Q000502:physiology; D002528:Cerebellar Neoplasms / Q000235:genetics*; D002531:Cerebellum / Q000166:cytology* / Q000502:physiology; D018507:Gene Expression Regulation, Developmental / Q000502:physiology*; D049452:Green Fluorescent Proteins / Q000235:genetics; D007150:Immunohistochemistry / Q000379:methods; D017403:In Situ Hybridization / Q000379:methods; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D046228:Microarray Analysis / Q000379:methods; D009369:Neoplasms / Q000235:genetics*; D009457:Neuroglia / Q000378:metabolism*; D009474:Neurons / Q000378:metabolism*; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*
D014157:Transcription Factors; D049452:Green Fluorescent Proteins