Abstract
The tuberal hypothalamic ventral premamillary nucleus (VPM) described in mammals links olfactory and metabolic cues with mating behavior and is involved in the onset of puberty. We offer here descriptive and experimental evidence on a migratory phase in the development of this structure in mice at E12.5–E13.5. Its cells originate at the retromamillary area (RM) and then migrate tangentially rostralward, eschewing the mamillary body, and crossing the molecularly distinct perimamillary band, until they reach a definitive relatively superficial ventral tuberal location. Corroborating recent transcriptomic studies reporting a variety of adult glutamatergic cell types in the VPM, and different projections in the adult, we found that part of this population heterogeneity emerges already early in development, during tangential migration, in the form of differential gene expression properties of at least 2–3 mixed populations possibly derived from subtly different parts of the RM. These partly distribute differentially in the core and shell parts of the final VPM. Since there is a neighboring acroterminal source of Fgf8, and Fgfr2 is expressed at the early RM, we evaluated a possible influence of Fgf8 signal on VPM development using hypomorphic Fgf8neo/null embryos. These results suggested a trophic role of Fgf8 on RM and all cells migrating tangentially out of this area (VPM and the subthalamic nucleus), leading in hypomorphs to reduced cellularity after E15.5 without alteration of the migrations proper.
Highlights
The hypothalamic tuberal ventral premamillary nucleus (VPM) was first identified by Gurdjian (1927). Canteras et al (1992) and Merlino et al (2019) studied its projections, which target the periaqueductal gray, the lateral tuberal area, the paraventricular hypothalamic nucleus, the preoptic area, various medial paraseptal BST nuclei, the ventral lateral septal nucleus and the amygdalo-hippocampal amygdalar nucleus
The retromamillary area (RM) and M subdomains are identifiable once neurogenesis begins, both by the bilateral large external bulge of the massive mamillary body, distinguishable as of E13.5–E14.5, and by their differential gene expression patterns: Foxb1, Nkx2.1, Unc5b, Nhlh2, and Sim1 are selectively expressed in the mamillary body, in contrast with the VPM markers mentioned above, expressed in the RM area (Foxa1, Nr4a2, Irx1, Irx5, Enc1, Lmx1b, Nos1, Pknox2; Supplementary Table 2)
In our phenotypic analysis of two available Fgf8neo/null severe hypomorph specimens we found a general reduction in the cellularity of the RM, VPM migration stream (VPMms) and VPM nucleus neurons, as well as of their subthalamic nucleus complex (STh)/parasubthalamic nucleus (PSTh) neighbors, mainly affecting the Foxa1 population
Summary
The hypothalamic tuberal ventral premamillary nucleus (VPM) was first identified by Gurdjian (1927). Canteras et al (1992) and Merlino et al (2019) studied its projections, which target the periaqueductal gray, the lateral tuberal area, the paraventricular hypothalamic nucleus, the preoptic area, various medial paraseptal BST nuclei, the ventral lateral septal nucleus and the amygdalo-hippocampal amygdalar nucleus. The VPM receives inputs from forebrain structures related to the vomeronasal system, conveying conspecific and heterospecific olfactory signals (Cavalcante et al, 2014) This nucleus apparently links signals of somatic energy balance and olfaction with mating behavior (Donato and Elias, 2011). The VPM appears as a relatively superficial ovoidal cell aggregate intercalated between the mamillary body and the hypophysial infundibulum, halfway between the ventromedial hypothalamic nucleus and the mamillary nucleus. It is separated from the latter by the histaminergic tuberomamillary area and the perimamillary band (the latter contains the conventional dorsal premamillary nucleus; DPM; Figure 1C). Its adult position is within the tuberal intermediate region in the basal plate of the terminal hypothalamus, dorsally to the topologically subjacent perimamillary and mamillary regions (PM; M; Figures 1C,E,G,H; Puelles et al, 2012)
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
