Multiple origins, migratory paths and molecular profiles of cells populating the avian interpeduncular nucleus

Abstract

The interpeduncular nucleus (IP) is a key limbic structure, highly conserved evolutionarily among vertebrates. The IP receives indirect input from limbic areas of the telencephalon, relayed by the habenula via the fasciculus retroflexus. The function of the habenulo-IP complex is poorly understood, although there is evidence that in rodents it modulates behaviors such as learning and memory, avoidance, reward and affective states. The IP has been an important subject of interest for neuroscientists, and there are multiple studies about the adult structure, chemoarchitecture and its connectivity, with complex results, due to the presence of multiple cell types across a variety of subnuclei. However, the ontogenetic origins of these populations have not been examined, and there is some controversy about its location in the midbrain-anterior hindbrain area. To address these issues, we first investigated the anteroposterior (AP) origin of the IP complex by fate-mapping its neuromeric origin in the chick, discovering that the IP develops strictly within isthmus and rhombomere 1. Next, we studied the dorsoventral (DV) positional identity of subpopulations of the IP complex. Our results indicate that there are at least four IP progenitor domains along the DV axis. These specific domains give rise to distinct subtypes of cell populations that target the IP with variable subnuclear specificity. Interestingly, these populations can be characterized by differential expression of the transcription factors Pax7, Nkx6.1, Otp, and Otx2. Each of these subpopulations follows a specific route of migration from its source, and all reach the IP roughly at the same stage. Remarkably, IP progenitor domains were found both in the alar and basal plates. Some IP populations showed rostrocaudal restriction in their origins (isthmus versus anterior or posterior r1 regions). A tentative developmental model of the structure of the avian IP is proposed. The IP emerges as a plurisegmental and developmentally heterogeneous formation that forms ventromedially within the isthmus and r1. These findings are relevant since they help to understand the highly complex chemoarchitecture, hodology and functions of this important brainstem structure.

Differentiation and molecular heterogeneity of inhibitory and excitatory neurons associated with midbrain dopaminergic nuclei

“…Nkx6-1 + cells have been previously described in the rostral part of the avian IPN (Lorente-Canovas et al, 2012). Consistent with this, numerous glutamatergic Nkx6-1 + Vsx2…”

“…S1E-Eb). This is also supported by gene expression and fate-mapping data from avian embryos (Lorente-Canovas et al, 2012). We found that some Pax7 + precursors co-expressed Zfpm2 but no other Gata-or Tal-related factors ( Fig.…”

Molecular analysis of the amphioxus frontal eye unravels the evolutionary origin of the retina and pigment cells of the vertebrate eye

“…Given that the PMC cells lie in the gbx expression region (54), and some of them also are positive for pax4/6 (Fig. 2F), their molecular identity resembles that of the vertebrate interpeduncular nucleus located in the hindbrain and involved in locomotor control (55). Taken together, these findings indicate that in amphioxus the frontal eye projects to the neurosecretory/tegmental neuropil and to the locomotor center, like the eye and the pineal gland in vertebrates.…”

Conserved localization of Pax6 and Pax7 transcripts in the brain of representatives of sarcopterygian vertebrates during development supports homologous brain regionalization

“…Subsequently during development, many cells appeared to migrate tangentially into the adjacent basal plate ( Figure 7O ) to reach the interpeduncular nucleus ( Figure 7P ). This situation is conserved through amniotes ( Figures 8D,H ), where Pax7 positive cells of the alar plate migrate into the basal plate during development to finally be a subpopulation of the interpeduncular complex (Lorente-Cánovas et al, 2012). …”

“…In developing amphibians, conspicuous Pax7 cell groups are widely distributed in the large r1, starting at early embryonic stages (Bandín et al, 2013; Joven et al, 2013b), like in birds and mammals (Aroca and Puelles, 2005). Comparatively, it is interesting to note that several neuronal populations were reported (in chick and mouse embryos) to be generated in the r1 alar plate, which migrate ventralwards into the medial basal plate, forming a sizeable part of the interpeduncular nucleus complex, apart other medial tegmental nuclei, along their migration pathway (Lorente-Cánovas et al, 2012; Moreno-Bravo et al, 2014). This migratory stream is exclusively present in r1 mantle (absent at isthmus proper and rest of rhombomeres) and was characterized as expressing Pax7, a transcription factor whose signal in the whole hindbrain is otherwise restricted to the alar ventricular zone (Ju et al, 2004).…”