Adult neural stem cells in distinct microdomains generate previously unknown interneuron types

• Published in: Nature neuroscience Vol. 17; no. 2; pp. 207 - 214
• Main Authors: Merkle, Florian T, Fuentealba, Luis C, Sanders, Timothy A, Magno, Lorenza, Kessaris, Nicoletta, Alvarez-Buylla, Arturo
• Format: Journal Article
• Language: English
• Published: New York Nature Publishing Group US 01.02.2014; Nature Publishing Group
• Subjects: 13/51; 14; 14/1; 14/19; 14/35; 631/136/368/2431; 631/378/2571/2578; 631/378/340; 631/532/2182; 64/110; 64/60; Adenoviruses; Age Factors; Animal Genetics and Genomics; Animals; Behavioral Sciences; Biological Techniques; Biology; Biomedicine; Brain research; Cerebral Ventricles - cytology; Cerebral Ventricles - growth & development; Gene Expression Regulation, Developmental - genetics; Gene Expression Regulation, Developmental - physiology; Glial Fibrillary Acidic Protein - genetics; Glial Fibrillary Acidic Protein - metabolism; Green Fluorescent Proteins - genetics; Green Fluorescent Proteins - metabolism; Homeodomain Proteins - genetics; Homeodomain Proteins - metabolism; Interneurons - classification; Interneurons - physiology; Kruppel-Like Transcription Factors - metabolism; Membrane Microdomains - physiology; Mice; Neural circuitry; Neural Stem Cells - cytology; Neurobiology; Neurogenesis; Neuroglia - physiology; Neurons; Neurosciences; Properties; RNA, Untranslated - metabolism; Stem cells; Transcription factors; Transcription Factors - genetics; Transcription Factors - metabolism; Transduction, Genetic; Zinc Finger Protein GLI1; San Francisco California; California; United Kingdom > UK; United States > US; Massachusetts
• ISSN: 1097-6256; 1546-1726
• DOI: 10.1038/nn.3610

The authors report the generation of four previously unknown olfactory bulb interneuron subtypes by adult neural stem cells, organized into surprisingly small progenitor microdomains. These microdomains appear to be defined by unique combinations of transcription factors not previously known to be involved in adult neurogenesis, including Nkx6.2 and Zic. Throughout life, neural stem cells (NSCs) in different domains of the ventricular-subventricular zone (V-SVZ) of the adult rodent brain generate several subtypes of interneurons that regulate the function of the olfactory bulb. The full extent of diversity among adult NSCs and their progeny is not known. Here, we report the generation of at least four previously unknown olfactory bulb interneuron subtypes that are produced in finely patterned progenitor domains in the anterior ventral V-SVZ of both the neonatal and adult mouse brain. Progenitors of these interneurons are responsive to sonic hedgehog and are organized into microdomains that correlate with the expression domains of the Nkx6.2 and Zic family of transcription factors. This work reveals an unexpected degree of complexity in the specification and patterning of NSCs in the postnatal mouse brain.