Ascl1 (previously Mash1) is a bHLH transcription factor essential for neuronal differentiation and specification in the nervous system. Although it has been studied for its role in several neural lineages, the full complement of lineages arising from Ascl1 progenitor cells remains unknown. Using an inducible Cre-flox genetic fate-mapping strategy, Ascl1 lineages were determined throughout the brain. Ascl1 is present in proliferating progenitor cells but these cells are actively differentiating as evidenced by rapid migration out of germinal zones. Ascl1 lineage cells contribute to distinct cell types in each major brain division: the forebrain including the cerebral cortex, olfactory bulb, hippocampus, striatum, hypothalamus, and thalamic nuclei, the midbrain including superior and inferior colliculi, and the hindbrain including Purkinje and deep cerebellar nuclei cells and cells in the trigeminal sensory system. Ascl1 progenitor cells at early stages in each CNS region preferentially become neurons, and at late stages they become oligodendrocytes. In conclusion, Ascl1-expressing progenitor cells in the brain give rise to multiple, but not all, neuronal subtypes and oligodendrocytes depending on the temporal and spatial context, consistent with a broad role in neural differentiation with some subtype specification.
Bibliographical noteFunding Information:
We are grateful for the outstanding technical assistance of T. Savage, J. Dumas, and Dr. K. Hori with special technical tips provided by Dr. R. Storm. We thank Dr. S. Dymecki for providing expertise in confirming anatomical structures in the brainstem. We also appreciate the generous gifts from Drs. T. Jessell for the anti-Lhx2/9 antibody, M. Wegner for the anti-Sox10 antibody, H. Edlund for the GST-Ptf1a expression construct, and E. Turner for the GST-Brn3a expression construct, and the Developmental Studies Hybridoma Bank developed under the auspices of the NICHD and maintained by The University of Iowa for providing monoclonal antibodies. This work was funded by NIH NS32817 to JEJ.
- Brain development
- Genetic fate mapping
- bHLH transcription factor