Abstract
BackgroundOlfactory bulb (OB) interneurons are known to represent diverse neuronal subtypes, which are thought to originate from a number of telencephalic regions including the embryonic dorsal lateral ganglionic eminence (dLGE) and septum. These cells migrate rostrally toward the OB, where they then radially migrate to populate different OB layers including the granule cell layer (GCL) and the outer glomerular layer (GL). Although previous studies have attempted to investigate regional contributions to OB interneuron diversity, few genetic tools have been used to address this question at embryonic time points when the earliest populations are specified.MethodsIn this study, we utilized Zic3-lacZ and Gsx2e-CIE transgenic mice as genetic fate-mapping tools to study OB interneuron contributions derived from septum and LGE, respectively. Moreover, to address the regional (i.e. septal) requirements of the homeobox gene Gsx2 for OB interneuron diversity, we conditionally inactivated Gsx2 in the septum, leaving it largely intact in the dLGE, by recombining the Gsx2 floxed allele using Olig2Cre/+ mice.ResultsOur fate mapping studies demonstrated that the dLGE and septum gave rise to OB interneuron subtypes differently. Notably, the embryonic septum was found to give rise largely to the calretinin+ (CR+) GL subtype, while the dLGE was more diverse, generating all major GL subpopulations as well as many GCL interneurons. Moreover, Gsx2 conditional mutants (cKOs), with septum but not dLGE recombination, showed impaired generation of CR+ interneurons within the OB GL. These Gsx2 cKOs exhibited reduced proliferation within the septal subventricular zone (SVZ), which correlated well with the reduced number of CR+ interneurons observed.ConclusionsOur findings indicate that the septum and LGE contribute differently to OB interneuron diversity. While the dLGE provides a wide range of OB interneuron subtypes, the septum is more restricted in its contribution to the CR+ subtype. Gsx2 is required in septal progenitors for the correct expansion of SVZ progenitors specified toward the CR+ subtype. Finally, the septum has been suggested to be the exclusive source of CR+ interneurons in postnatal studies. Our results here demonstrate that dLGE progenitors in the embryo also contribute to this OB neuronal subtype.
Highlights
Olfactory bulb (OB) interneurons are known to represent diverse neuronal subtypes, which are thought to originate from a number of telencephalic regions including the embryonic dorsal lateral ganglionic eminence and septum
We observed that β-galactosidase from Zic3-lacZ transgene was largely restricted to the Zic+ medial telencephalon, with only a few scattered cells occasionally observed in the ventricular zone (VZ) of the rostroventral lateral ganglionic eminence (LGE) (Fig. 1A-G)
A gradient of βgal staining was noticeable in the septal VZ, which was more uniform in the dorsal septum (Fig. 1A-G)
Summary
Olfactory bulb (OB) interneurons are known to represent diverse neuronal subtypes, which are thought to originate from a number of telencephalic regions including the embryonic dorsal lateral ganglionic eminence (dLGE) and septum. These cells migrate rostrally toward the OB, where they radially migrate to populate different OB layers including the granule cell layer (GCL) and the outer glomerular layer (GL). Olfactory bulb (OB) interneurons represent a highly diverse neuronal population that serve as important components in the relay of olfactory signals from the environment to the brain [1] They are largely inhibitory and modulate local projection neuron activity by releasing gamma-aminobutyric acid (GABA) [2, 3]. The specific roles of the diverse OB interneuron subtypes in olfactory circuits is not well defined, studies have shown these interneurons originate from the embryonic ventral telencephalon and regional progenitor domains in the postnatal SVZ [2, 8, 9, 10]
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