Regional differences in mitral cell development in mouse olfactory bulb

Abstract

Olfactory sensory neurons (OSNs) located in the dorsomedial and ventromedial regions of the olfactory epithelium (OE) are distinguished from one another based on their molecular expression patterns. This difference is reflected in the separation of the glomerular layer of the olfactory bulb (OB) into dorsomedial and ventrolateral regions. However, it is unclear whether a complementary separation is also evident in the projection neurons that innervate the OB glomeruli. In this study, we compared the development of the OB between different regions by focusing on the transcription factor, Tbx21, which is expressed by mitral and tufted cells in the mature OB. Examining the OB at different developmental ages, we found that Tbx21 expression commenced in the anteromedial region called the tongue‐shaped area, followed by the dorsomedial and then ventrolateral areas. We also showed that the tongue‐shaped area was innervated by the OSNs located in the most dorsomedial part of the ventrolateral OE, the V‐zone:DM. Interestingly, the generation of OSNs occurred first in the dorsomedial zone including the V‐zone:DM, suggesting a correlation between the time course of OSN generation in the OE and Tbx21 expression in their target region of the OB. In contrast, expression of vGluT1, which is also found in all mitral cells in the mature OB, was first detected in the ventrolateral region during development. Our findings demonstrate that the development of projection neurons occurs in a compartmentalized manner in the OB; tongue‐shaped, dorsomedial, and ventrolateral areas, and that not all projection neurons follow the same developmental pathway.

Topographically Distinct Projection Patterns of Early-Generated and Late-Generated Projection Neurons in the Mouse Olfactory Bulb

“…Of note, we reported that Tbr1 expression preceded Tbr2 in developing mitral cell (Imamura and Greer, 2013), suggesting that mitral cells follow a non-canonical pathway of differentiation in contrast to that described for cortical pyramidal neurons in which Tbr2 is expressed prior to Tbr1 during development (Englund et al, 2005). In addition, we and others demonstrated that each transcription factor appears in the developing OB with a distinct spatiotemporal pattern (Williams et al, 2007;Campbell et al, 2011;Nguyen and Imamura, 2019). Thus, comparing the types and time course of transcription factor expression among OB projection neurons generated at different time points during development is critical to understand the molecular mechanisms underlying the generation of OB projection neuron diversity.…”

“…To compare the axonal projection patterns of OB projection neurons generated at different developmental stages, we electroporated pCALNL-GFP into the brains of Tbx21Cre x tdTomato transgenic mice. In these mice, tdTomato is expressed by all OB projection neurons (Nguyen and Imamura, 2019). Our previous studies showed that differences in cell body location and dendrite extension patterns between E11-and E12-generated mitral cells were greater than those between E10-and E11-generated mitral cells (Imamura et al, 2011;Imamura and Greer, 2015).…”

“…The offspring of CD1 female mice (Charles River; Wilmington, MA; strain code 022; RRID:IMSR_CRL:022) mated with the Tbx21-Cre (B6;CBA-Tg (Tbx21-cre)1Dlc/J; The Jackson Laboratory; Bar Arbor, ME; stock #024507; RRID:IMSR_JAX:024507) (Haddad et al, 2013) or Tbx21Cre x tdTomato male mice were used for the in utero electroporation in this study. The Tbx21Cre x tdTomato line was created by crossing Tbx21-Cre mice with B6.Cg-Gt(ROSA)26Sortm9 (CAG-tdTomato) Hze/J reporter mice (The Jackson Laboratory; stock #007909; RRID:IMSR_JAX:007909) (Nguyen and Imamura, 2019). The day on which we found a copulation plug was called E0, and the succeeding days of gestation were numbered in order.…”

“…However, the electroporation also delivers the plasmids into some interneurons in the OB as well as neurons in the other brain regions including the AON, OT, and PIR, which makes it difficult to analyze the axonal projection patterns of OB projection neurons to the olfactory cortex. To overcome this difficulty, we used the Tbx21-Cre transgenic mice in which the Cre recombinase expression is controlled by the Tbx21 promoter (Haddad et al, 2013;Nguyen and Imamura, 2019). Since Tbx21 is exclusively expressed by OB projection neurons in the mouse brain (Mitsui et al, 2011), this method ensures that GFP expression will occur only in OB projection neurons by electroporating the plasmid, pCALNL-GFP, which expresses GFP upon the presence of Cre recombinase (Fig.…”

Mitral cell development in the olfactory bulb of sharks: evidences of a conserved pattern of glutamatergic neurogenesis

“…On the other hand, in mammals, NeuroD expression pattern also overlapped Tbr2 expression, but not Tbr1 expression, indicating the existence of subsets of mitral cells (Roybon et al 2015). Besides, recent studies show that maturation of mitral cells depends on their position in the developing OB (Nguyen and Imamura 2019). Some studies in elasmobranchs based on Golgi staining have evidenced the existence of two kind of mitral cells in the OB of the sharks studied ( Sphyrna tiburo, Dasyatis sabina and Rhizoprionodon terranovae) : mitral cells with dense and tight arborized dendrites and mitral cells with a loose dendrite arborization (Dryer and Graziadei 1993).…”