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Isolation of Targeted Hypothalamic Neurons for Studies of Hormonal, Metabolic, and Electrical Regulation
Published on: August 4, 2023
Development of posterior hypothalamic neurons enlightens a switch in the prosencephalic basic plan.
Sophie Croizier1, Clotilde Amiot, Xiaoping Chen
1EA3922, Faculté de Médecine et de Pharmacie, Université de Franche-Comté, Besançon, France.
Plos One
|December 24, 2011
Summary
Melanin-concentrating hormone (MCH) neurons in the hypothalamus project to the brain and spinal cord. Early MCH neuron development and axon guidance involve specific genes and signaling pathways.
Area of Science:
- Neuroscience
- Developmental Biology
- Molecular Biology
Background:
- Melanin-concentrating hormone (MCH) neurons project widely in the brain, including to the cerebral cortex and spinal cord.
- These projections arise from distinct MCH neuron subpopulations, some expressing Cocaine-and-Amphetamine-Regulated Transcript (CART) peptide.
- The early development and axonal pathways of MCH neurons are not fully understood.
Purpose of the Study:
- To investigate the developmental origin and early axonal trajectory of MCH neurons in rats and mice.
- To identify the molecular mechanisms guiding the initial growth of MCH axons.
- To understand the relationship between MCH neuron development and broader prosencephalic organization.
Main Methods:
- Utilized Bromodeoxyuridine (BrdU) labeling to trace the birthdating of MCH neurons.
- Examined the expression patterns of regulatory genes like Sonic hedgehog (Shh) and Nkx2.2 during development.
- Analyzed the expression and function of guidance molecules such as Netrin1 and Slit2.
Main Results:
- MCH neurons are among the earliest generated in the hypothalamus, originating from a longitudinal cell cord expressing Shh and Nkx2.2.
- The first MCH axons navigate through the tractus postopticus (tpoc), following a path parallel to the Shh/Nkx2.2 expression domain.
- Ascending MCH axons co-migrate with dopaminergic axons within the medial forebrain bundle (mfb), influenced by Netrin1 and Slit2 signaling.
- Later-developing MCH neurons and axons emerge as general neurogenesis and differentiation occur in the prosencephalon.
Conclusions:
- The earliest MCH neurons develop within a specific diencephalic segment of a Shh/Nkx2.2-expressing neurogenic column.
- The developing telencephalon and expanding medial forebrain bundle influence the organization and trajectory of MCH projections.
- This study elucidates critical developmental events and molecular cues governing MCH system formation.
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