Abstract
Tegmental nuclei in the ventral midbrain and anterior hindbrain control motivated behavior, mood, memory, and movement. These nuclei contain inhibitory GABAergic and excitatory glutamatergic neurons, whose molecular diversity and development remain largely unraveled. Many tegmental neurons originate in the embryonic ventral rhombomere 1 (r1), where GABAergic fate is regulated by the transcription factor (TF) Tal1. We used single-cell mRNA sequencing of the mouse ventral r1 to characterize the Tal1-dependent and independent neuronal precursors. We describe gene expression dynamics during bifurcation of the GABAergic and glutamatergic lineages and show how active Notch signaling promotes GABAergic fate selection in post-mitotic precursors. We identify GABAergic precursor subtypes that give rise to distinct tegmental nuclei and demonstrate that Sox14 and Zfpm2, two TFs downstream of Tal1, are necessary for the differentiation of specific tegmental GABAergic neurons. Our results provide a framework for understanding the development of cellular diversity in the tegmental nuclei.
Highlights
The anterior brainstem is a complex brain region that comprises anatomically and functionally distinct tegmental nuclei regulating vital processes
We identify GABAergic precursor subtypes that give rise to distinct tegmental nuclei and demonstrate that Sox14 and Zfpm2, two transcription factor (TF) downstream of Tal1, are necessary for the differentiation of specific tegmental GABAergic neurons
As Tal1-dependent GABAergic precursors are born in the ventral r1 at embryonic day 10.5 (E10.5) to E13.5 and move to their final destinations shortly thereafter (Achim et al, 2012; Lahti et al, 2016), we profiled the cell types undergoing neurogenesis
Summary
The anterior brainstem is a complex brain region that comprises anatomically and functionally distinct tegmental nuclei regulating vital processes. Some of the ventral brainstem neurons, such as glutamatergic neurons in the reticular activating system, originate in the dorsal r1, including the rhombic lip (Aroca et al, 2006; Green and Wingate, 2014; Lorente-Canovas et al, 2012; Machold and Fishell, 2005; Rose et al, 2009). GABAergic neurons in the interpeduncular nucleus (IPN) and medial brainstem area undergo migrations from the dorsolateral r1 (Lorente-Canovas et al, 2012; Waite et al, 2012). In the rV2 region, proliferative neuronal progenitors expressing the transcription factor (TF) Nkx give rise to intermingled post-mitotic precursors of both
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
