Development of Posterior Hypothalamic Neurons Enlightens a Switch in the Prosencephalic Basic Plan

Abstract

In rats and mice, ascending and descending axons from neurons producing melanin-concentrating hormone (MCH) reach the cerebral cortex and spinal cord. However, these ascending and descending projections originate from distinct sub-populations expressing or not “Cocaine-and-Amphetamine-Regulated-Transcript” (CART) peptide. Using a BrdU approach, MCH cell bodies are among the very first generated in the hypothalamus, within a longitudinal cell cord made of earliest delaminating neuroblasts in the diencephalon and extending from the chiasmatic region to the ventral midbrain. This region also specifically expresses the regulatory genes Sonic hedgehog (Shh) and Nkx2.2. First MCH axons run through the tractus postopticus (tpoc) which gathers pioneer axons from the cell cord and courses parallel to the Shh/Nkx2.2 expression domain. Subsequently generated MCH neurons and ascending MCH axons differentiate while neurogenesis and mantle layer differentiation are generalized in the prosencephalon, including telencephalon. Ascending MCH axons follow dopaminergic axons of the mesotelencephalic tract, both being an initial component of the medial forebrain bundle (mfb). Netrin1 and Slit2 proteins that are involved in the establishment of the tpoc and mfb, respectively attract or repulse MCH axons.We conclude that first generated MCH neurons develop in a diencephalic segment of a longitudinal Shh/Nkx2.2 domain. This region can be seen as a prosencephalic segment of a medial neurogenic column extending from the chiasmatic region through the ventral neural tube. However, as the telencephalon expends, it exerts a trophic action and the mfb expands, inducing a switch in the longitudinal axial organization of the prosencephalon.

Tobacco Smoke-Induced Brain White Matter Myelin Dysfunction: Potential Co-Factor Role of Smoking in Neurodegeneration

“…FOXO1 and FOXO4 target insulin signaling [96]. NKX2-2 and NKX6-1 cooperate in regulating regions of axon guidance and support insulin-producing cells [97], myelin maturation from OPCs [98], and genes that have important roles in axonal guidance [99]. Therefore, at least with respect to FOXO4 and NKX6, CS8/CS8 + R could adversely affect the regulation of insulin-mediated functions in the brain.…”

Ablation of Neurons Expressing Melanin-Concentrating Hormone (MCH) in Adult Mice Improves Glucose Tolerance Independent of MCH Signaling

“…Our method for ablating MCH neurons allowed temporal control; in the current study, MCH neurons were ablated in adulthood, and glucose tolerance was tested within 2 weeks. In the embryo, MCH neurons differentiate early (Risold et al, 2009), and recent evidence suggests that some phenotypes of congenital MCH deficiency arise from alterations during development (Mul et al 2010; Croizier et al, 2011). In the study by Kong et al, MCH neurons were insensitive to glucose during this time, and glucose tolerance was tested months later, after chronic absence of glucose sensitivity in MCH neurons.…”

Development of the hypothalamus: conservation, modification and innovation

“…In the prosomeric model, this boundary separates the anterior and tuberal hypothalamus, whereas the columnar model places the boundary parallel to the anterior/posterior (A/P) axis, spanning all compartments . While the prosomeric model supports hypotheses relating hypothalamic and telencephalic co-evolution (Croizier et al, 2011), it has been challenged by experimental evidence from gene expression and function (Bedont et al, 2015). Additional comparative studies will be needed to shed further light on this fundamental anatomical question.…”

“…Another example is Otp, where its zebrafish orthologs and upstream regulator fezf2 are also required for hypothalamic dopaminergic neurogenesis, whereas mouse Otp and Fezf2 are not (Levkowitz et al, 2003;Blechman et al, 2007;Ryu et al, 2007;Shimizu and Hibi, 2009). This species-specific circuitry has been proposed to represent a neofunctionalization of the ancestral cell type to allow more complex behavioral control that is coordinated with structural evolution of the brain (Croizier et al, 2011).…”