Dbx1-Derived Pyramidal Neurons Are Generated Locally in the Developing Murine Neocortex

Abstract

The neocortex (NCx) generates at the dorsal region of the pallium in the forebrain. Several adjacent structures also contribute with neurons to NCx. Ventral pallium (VP) is considered to generate several populations of neurons that arrive through tangential migration to the NCx. Amongst them are the Cajal-Retzius cells and some transient pyramidal neurons. However, the specific site and timing of generation, trajectory of migration and actual contribution to the pyramidal population remains elusive. Here, we investigate the spatio-temporal origin of neuronal populations from VP in an in vivo model, using a transposase mediated in utero electroporation method in embryonic mouse. From E11 to E14 cells born at the lateral corner of the neocortical neuroepithelium including the VP migrated ventro-laterally to settle all areas of the ventral telencephalon. Specifically, neurons migrated into amygdala (Ag), olfactory cortices, and claustrum (Cl). However, we found no evidence for any neurons migrating tangentially toward the NCx, regardless the antero-posterior level and developmental time of the electroporation. Our results challenge the described ventral-pallial origin of the transient pyramidal neuron population. In order to find the exact origin of cortical neurons that were previously Dbx1-fate mapped we used the promoter region of the murine Dbx1 locus to selectively target Dbx1-expressing progenitors and label their lineage. We found these progenitors in low numbers in all pallial areas, and not only in the ventral pallial ventricular zone. Our findings on the local cortical origin of the Dbx1-derived pyramidal neurons reconcile the observation of Dbx1-derived neurons in the cortex without evidence of dorsal tangential migration from VP and provide a new framework for the origin of the transient Dbx1-derived pyramidal neuron population. We conclude that these neurons are born locally within the dorsal pallial neuroepithelium.

In search of common developmental and evolutionary origin of the claustrum and subplate

“…These data were derived from the Allen Brain Atlas Data Portal (ABADP) resources available in the public domain: (http://help.brain-map.org/pages/viewpage.action?pageId=2424836). The data that support the findings of Figures 6 and 7 are based on the datasets partially published by García‐Moreno et al (2018; https://doi.org/10.1016/j.celrep.2017.12.032) and Rueda‐Alaña et al (2018; https://doi.org/10.3389/fnins.2018.00792) available from the corresponding author upon reasonable request. The data that support the findings of Figure 8 are based on the datasets published by Hoerder‐Suabedissen et al (2018; https://doi.org/10.1093/cercor/bhy036) and available from the corresponding author upon reasonable request.…”

“…However, no direct lineage tracing study has been performed so far confirming this hypothesis. Our preliminary focal electroporation studies examining the VPall and LPall revealed no dorsally migrating subplate neurons from VPall and LPall electroporations in the embryonic mouse (Figure 6; García‐Moreno et al, 2018; Rueda‐Alaña, Martínez‐Garay, Encinas, Molnár, & García‐Moreno, 2018; García‐Moreno, Molnár unpublished observations). Since Puelles' hypothesis postulates a restricted early LPall origin of the dorsally migrating subplate neurons (Puelles, 2014), these experiments have to be repeated with selectively targeting LPall at early stages (E11).…”

“…In utero electroporation of the lateral pallium at E12 labels overlying neurons of the insular cortex but no cells migrating dorsally toward the neocortex and subplate (Figure 6d; Rueda‐Alaña et al, 2018). This is consistent with previous hypotheses stating that both the claustrum and EPd arise from the early lateral pallium, with the claustrum migrating first along the insular cortex pathway whereas the EPd neurons would migrate tangentially ventrally out of lateral pallium into VPall, to localize deep to the VPall‐derived piriform cortex (Puelles, 2014; Rueda‐Alaña et al, 2018; Watson & Puelles, 2017).…”

“…Scale bars 500 μm for (c) and (d) and 50 μm for high power panels on the right. For technical details see original articles by García‐Moreno et al (2018) and Rueda‐Alaña et al (2018) [Color figure can be viewed at wileyonlinelibrary.com]…”

Evolution of Pallial Areas and Networks Involved in Sociality: Comparison Between Mammals and Sauropsids

“…Developmental studies, particularly those on combinatorial expression patterns of early regulatory genes in relation to the topological framework of the neural tube, have become extremely useful to unravel the brain morphoplan, with its basic divisions comparable across vertebrates (Nieuwenhuys and Puelles, 2016). The conclusions of this type of approach support that a large lateroventral part of the avian and reptilian pallium (called the dorsal ventricular ridge) derives from pallial embryonic divisions that gives rise to the pallial amygdala and other areas of the so-called piriform lobe in mammals (Puelles et al, 2000, 2017; Medina et al, 2011, 2017a; Abellán et al, 2013; Desfilis et al, 2018), a proposal also supported by results of fate mapping (Hirata et al, 2009; Soma et al, 2009; Waclaw et al, 2010; Bupesh et al, 2011; Puelles et al, 2016a; García-Moreno et al, 2018; Rueda-Alaña et al, 2018), tract-tracing studies (Bruce and Neary, 1995; Martínez-García et al, 2007), and more recently, by single-cell transcriptome (Tosches et al, 2018). In this account, we will review the different data pointing to the presence of a pallial amygdala-like region in the sauropsidian dorsal ventricular ridge, as well as the possible existence of an area comparable to the orbitofrontal cortex.…”