Thumbnail
Access Restriction
Open

Author Brown, Ashly ♦ Machan, Jason T. ♦ Hayes, Lindsay ♦ Zervas, Mark
Source World Health Organization (WHO)-Global Index Medicus
Content type Text
Publisher Wiley
File Format HTM / HTML
Language English
Difficulty Level Medium
Subject Domain (in DDC) Natural sciences & mathematics ♦ Chemistry & allied sciences ♦ Life sciences; biology ♦ Physiology & related subjects ♦ Biochemistry ♦ Natural history of organisms ♦ Technology ♦ Medicine & health ♦ Human anatomy, cytology, histology ♦ Human physiology ♦ Pharmacology and therapeutics ♦ Diseases
Subject Domain (in MeSH) Nervous System ♦ Cells ♦ Embryonic Structures ♦ Anatomy ♦ Eukaryota ♦ Organisms ♦ Organic Chemicals ♦ Hormones, Hormone Substitutes, and Hormone Antagonists ♦ Amino Acids, Peptides, and Proteins ♦ Chemicals and Drugs ♦ Cell Physiological Phenomena ♦ Biological Sciences
Subject Keyword Discipline Neurology ♦ Dopamine ♦ Metabolism ♦ Mesencephalon ♦ Cytology ♦ Neurons ♦ Physiology ♦ Stem Cells ♦ Wnt1 Protein ♦ Animals ♦ Cell Lineage ♦ Embryo, Mammalian ♦ Drug Effects ♦ Estrogen Antagonists ♦ Pharmacology ♦ Embryology ♦ Mice ♦ Mice, Transgenic ♦ Recombinant Fusion Proteins ♦ Genetics ♦ Tamoxifen ♦ Journal Article ♦ Research Support, N.i.h., Extramural ♦ Research Support, Non-u.s. Gov't
Abstract Midbrain dopamine (MbDA) neurons are functionally heterogeneous and modulate complex functions through precisely organized anatomical groups. MbDA neurons are generated from Wnt1-expressing progenitors located in the ventral mesencephalon (vMes) during embryogenesis. However, it is unclear whether the progenitor pool is partitioned into distinct cohorts based on molecular identity and whether the timing of gene expression uniquely identifies subtypes of MbDA neurons. In this study we show that Wnt1-expressing MbDA progenitors from embryonic day (E)8.5-12.5 have dynamic molecular identities that correlate with specific spatial locations in the vMes. We also tested the hypothesis that the timing of Wnt1 expression in progenitors is related to the distribution of anatomically distinct cohorts of adult MbDA neurons using genetic inducible fate mapping (GIFM). We demonstrate that the Wnt1 lineage contributes to specific cohorts of MbDA neurons during a 7-day epoch and that the contribution to MbDA neurons predominates over other ventral Mb domains. In addition, we show that calbindin-, GIRK2-, and calretinin-expressing MbDA neuron subtypes are derived from Wnt1-expressing progenitors marked over a broad temporal window. Through GIFM and quantitative analysis we demonstrate that the Wnt1 lineage does not undergo progressive lineage restriction, which eliminates a restricted competence model of generating MbDA diversity. Interestingly, we uncover that two significant peaks of Wnt1 lineage contribution to MbDA neurons occur at E9.5 and E11.5. Collectively, our findings delineate the temporal window of MbDA neuron generation and show that lineage and timing predicts the terminal distribution pattern of MbDA neurons.
Description Country affiliation: United States
Author Affiliation: Brown A ( Department of Neuroscience, Brown University, Providence, Rhode Island 02903, USA.)
ISSN 00219967
Educational Role Student ♦ Teacher
Age Range above 22 year
Educational Use Reading ♦ Research ♦ Self Learning
Interactivity Type Expositive
Education Level UG and PG
Learning Resource Type Article
Publisher Date 2011-10-15
Publisher Place United States
e-ISSN 10969861
Journal Journal of Comparative Neurology
Volume Number 519
Issue Number 15


Source: WHO-Global Index Medicus