Sim1-expressing cells illuminate the origin and course of migration of the nucleus of the lateral olfactory tract in the mouse amygdala

Abstract

We focus this report on the nucleus of the lateral olfactory tract (NLOT), a superficial amygdalar nucleus receiving olfactory input. Mixed with its Tbr1-expressing layer 2 pyramidal cell population (NLOT2), there are Sim1-expressing cells whose embryonic origin and mode of arrival remain unclear. We examined this population with Sim1-ISH and a Sim1-tauLacZ mouse line. An alar hypothalamic origin is apparent at the paraventricular area, which expresses Sim1 precociously. This progenitor area shows at E10.5 a Sim1-expressing dorsal prolongation that crosses the telencephalic stalk and follows the terminal sulcus, reaching the caudomedial end of the pallial amygdala. We conceive this Sim1-expressing hypothalamo-amygdalar corridor (HyA) as an evaginated part of the hypothalamic paraventricular area, which participates in the production of Sim1-expressing cells. From E13.5 onwards, Sim1-expressing cells migrated via the HyA penetrate the posterior pallial amygdalar radial unit and associate therein to the incipient Tbr1-expressing migration stream which swings medially past the amygdalar anterior basolateral nucleus (E15.5), crosses the pallio-subpallial boundary (E16.5), and forms the NLOT2 within the anterior amygdala by E17.5. We conclude that the Tbr1-expressing NLOT2 cells arise strictly within the posterior pallial amygdalar unit, involving a variety of required gene functions we discuss. Our results are consistent with the experimental data on NLOT2 origin reported by Remedios et al. (Nat Neurosci 10:1141–1150, 2007), but we disagree on their implication in this process of the dorsal pallium, observed to be distant from the amygdala.

Development of the mouse anterior amygdalar radial unit marked by Lhx9-expression

“…Remarkably, they did not recognize Dbx1 progeny at nuclei derived from the posterior unit (AHi/PMCo). However, with more experience of amygdalar structure than we had then (due to our work in , 2021, and present report), we would reinterpret the labelled cell mass which Puelles et al (2016a) tagged as 'MePV' in their Fig. 2d (E14.5) as corresponding to the AHi/PMCo complex, found caudal to the MePV proper.…”

“…3 of Puelles and Rubenstein, 2003, and Fig. 10 of Puelles and Rubenstein 2015; recently we proposed to call it the hypothalamo-amygdalar corridor or HyA; Garcia-Calero et al 2021). Note Dbx1-derived progeny clearly appears periventricularly at the floor of the terminal sulcus in E14.5 embryos, as shown by Puelles et al (2016a) in their Figs.…”

“…This transcription factor may have redundant functions at this locus with respect to Lhx9 (Remedios et al 2004). On the other hand, loss of function of Lhx2 reportedly produces lack of migration of the NLOT2 nucleus (Remedios et al 2007; see also Garcia-Calero et al 2021, where we deal specifically with this migration).…”

“…First, Puelles et al (2019) and deduced from the concentric ring model of the telencephalic cortical pallium and correlative molecular mappings that the pallial amygdala is wholly external in nature to the whole cortex-like pallium and thus should be considered histogenetically independent as a separate amygdalar pallium field (a point that was unclear before; most authors tended to assume that amygdalar populations were produced within given cortical pallial sectors and thereafter migrated tangentially to their final amygdalar sites, though such migrations were not demonstrated; see Deussing and Wurst 2007). Puelles et al (2019) and Garcia-Calero et al (2021) expressed doubts about a dorsopallial origin of the amygdalar NLOT nucleus (postulated by Remedios et al 2007) due to inconsistency of this notion within the concentric ring model (i.e., there is no dorsal pallium next to the separate amygdalar pallial neighbourhood). Secondly, we recently examined the radial (glial) dimension of the mouse pallial amygdala, aiming to identify its intrinsic radial histogenetic subdivisions, and clarify the ascription of individual amygdalar nuclei relative to periventricular, intermediate or superficial strata within these units .…”

Novel Perspectives on the Development of the Amygdala in Rodents

“…Notably, CoupTf2 expression in both pallial and subpallial progenitor zones of the amygdala has been reported in chicken, and in sauropsids two CoupTf2- positive pallial divisions have been identified, with strongest expression reported in the caudalmost division, strikingly comparable to the strong CoupTf2 expression in the more caudal mouse pallial amygdalar units (reviewed in Medina et al, 2021 ). Peculiarly, a subset of hypothalamus-derived cells ( Sim1 +, Otp- ), originating in the supraopto-paraventricular hypothalamus (SVP), was found to populate a shell-shaped region surrounding the BMA nucleus at its medial side ( Figure 3 ; García-Moreno et al, 2010 ; Garcia-Calero et al, 2021 ; Morales et al, 2021 ).…”