Genetic Inducible Fate Mapping (GIFM) and the Conditional Deletion of Neurog1 in the Developing Mouse Cerebellum
Abstract
During neural development, proliferation and maturation of progenitor cells is regulated so neuronal cell types are generated in a controlled spatio-temporal sequence. The transcriptional programs driving diverse GABAergic neuron populations from their common progenitor pools in the developing cerebellum remain unclear. Neurog1 is a proneural basic helix-loop-helix (bHLH) transcription factor expressed in progenitor cells in the ventricular zone (VZ) of embryos and subsequently in the presumptive white matter (pWM) tracts of developing postnatal mice. We used genetic inducible fate mapping (GIFM) with a transgenic Neurog1-CreER allele to characterize contributions of Neurog1 lineages to the cerebellum of mice. Neurog1-expressing progenitors are fate-mapped to become Purkinje cells (PCs) and all inhibitory interneuron cell types of the cerebellar cortex but not glia. PCs are labeled between embryonic days (E)10.5 to E12.5 and GABAergic interneurons are labeled between E11.5 to postnatal day (P)7 with their final resting position following an inside-to-outside pattern in the cerebellar cortex. Long-term BrdU retention of GIFM lineages reveals PCs express Neurog1 around the time they become post-mitotic, in contrast to Neurog1 expression in 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. As conventional Neurog1Neo knockout mice are neonatal lethal, we generated Neurog1loxPmutant mice to examine the effects of conditional Neurog1 deletion on postnatal development in the cerebellum. Targeted Neurog1 loss-of-function does not result in significant differences in cerebellar morphology or number of GABAergic neurons in the cerebellar cortex of P21 mice. We quantified rates of cell proliferation and cell cycle progression or re-entry in embryonic Neurog1Neo and postnatal Neurog1loxP knockouts.
Document Details
- Document Type
- Technical Report
- Publication Date
- May 18, 2018
- Accession Number
- AD1128563
Entities
People
- Edwin A. Obana
Organizations
- Uniformed Services University of the Health Sciences