title: Neurog1 Genetic Inducible Fate Mapping (GIFM) Reveals the Existence of Complex Spatiotemporal Cyto-Architectures in the Developing Cerebellum.
abstract: Neurog1 is a pro-neural basic helix-loop-helix (bHLH) transcription factor expressed in progenitor cells located in the ventricular zone and subsequently the presumptive white matter tracts of the developing mouse cerebellum. We used genetic inducible fate mapping (GIFM) with a transgenic Neurog1-CreER allele to characterize the contributions of Neurog1 lineages to cerebellar circuit formation in mice. GIFM reveals Neurog1-expressing progenitors are fate-mapped to become Purkinje cells and all GABAergic interneuron cell types of the cerebellar cortex but not glia. The spatiotemporal sequence of GIFM is unique to each neuronal cell type. GIFM on embryonic days (E) 10.5 to E12.5 labels Purkinje cells with different medial-lateral settling patterns depending on the day of tamoxifen delivery. GIFM on E11.5 to P7 labels interneurons and the timing of tamoxifen administration correlates with the final inside-to-outside resting position of GABAergic interneurons in the cerebellar cortex. Proliferative status and long-term BrdU retention of GIFM lineages reveals Purkinje cells express Neurog1 around the time they become post-mitotic. In contrast, GIFM labels mitotic and post-mitotic interneurons. Neurog1-CreER GIFM reveals a correlation between the timing of Neurog1 expression and the spatial organization of GABAergic neurons in the cerebellar cortex with possible implications for cerebellar circuit assembly.
authors.affiliation: Department of Anatomy, Physiology and Genetics, Center for Neuroscience and Regenerative Medicine (CNRM), Uniformed Services University of the Health Sciences, 4301 Jones Bridge Road, Bethesda, MD, 20814, USA.
authors.forename: Edwin A
authors.initials: EA
authors.lastname: Obana
authors.forename: Travis G
authors.initials: TG
authors.lastname: Lundell
authors.forename: Kevin J
authors.initials: KJ
authors.lastname: Yi
authors.forename: Kryslaine L
authors.initials: KL
authors.lastname: Radomski
authors.forename: Qiong
authors.initials: Q
authors.lastname: Zhou
authors.forename: Martin L
authors.initials: ML
authors.lastname: Doughty
mesh_terms: D000818:Animals; D051792:Basic Helix-Loop-Helix Proteins / Q000235:genetics*; D001931:Brain Mapping / Q000379:methods; D001973:Bromodeoxyuridine / Q000378:metabolism; D002454:Cell Differentiation / Q000502:physiology; D019070:Cell Lineage / Q000235:genetics / Q000502:physiology; D002531:Cerebellum / Q000166:cytology* / Q000378:metabolism; D004965:Estrogen Antagonists / Q000494:pharmacology; D005260:Female; D018507:Gene Expression Regulation, Developmental / Q000235:genetics*; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D007395:Interneurons / Q000166:cytology / Q000378:metabolism*; D051379:Mice; D008822:Mice, Transgenic; D009419:Nerve Tissue Proteins / Q000235:genetics*; D011247:Pregnancy; D011689:Purkinje Cells / Q000166:cytology / Q000378:metabolism*; D013234:Stem Cells / Q000166:cytology* / Q000378:metabolism; D013629:Tamoxifen / Q000494:pharmacology; D013997:Time Factors
chemical_list: D051792:Basic Helix-Loop-Helix Proteins; D001973:Bromodeoxyuridine; D004965:Estrogen Antagonists; D009419:Nerve Tissue Proteins; D013629:Tamoxifen; C486336:Neurog1 protein, mouse