The Mouse Homeobox GeneGbx2Is Required for the Development of Cholinergic Interneurons in the Striatum
| Autor: | James Y. H. Li, Li Chen, Mallika Chatterjee |
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| Rok vydání: | 2010 |
| Předmět: |
Male
Ganglionic eminence Neurogenesis Mice Transgenic Striatum Biology Article Mice Neural Stem Cells Cell Movement Interneurons Animals Cell Lineage Gene Knock-In Techniques Cholinergic neuron Homeodomain Proteins Mice Knockout Basal forebrain General Neuroscience Gene Expression Regulation Developmental Cell Differentiation Acetylcholine Neural stem cell Neostriatum nervous system Forebrain Cholinergic Female Neuroscience |
| Zdroj: | The Journal of Neuroscience. 30:14824-14834 |
| ISSN: | 1529-2401 0270-6474 |
| DOI: | 10.1523/jneurosci.3742-10.2010 |
| Popis: | Mammalian forebrain cholinergic neurons are composed of local circuit neurons in the striatum and projection neurons in the basal forebrain. These neurons are known to arise from a common pool of progenitors that primarily resides in the medial ganglionic eminence (MGE). However, little is known about the genetic programs that differentiate these two types of cholinergic neurons. Using inducible genetic fate mapping, here we examined the developmental fate of cells that express the homeodomain transcription factor Gbx2 in the MGE. We show that theGbx2lineage-derived cells that undergo tangential migration exclusively give rise to almost all cholinergic interneurons in the striatum, whereas those undergoing radial migration mainly produce noncholinergic neurons in the basal forebrain. Deletion ofGbx2throughout the mouse embryo or specifically in the MGE results in abnormal distribution and significant reduction of cholinergic neurons in the striatum. We show that early-born (before embryonic day 12.5) cholinergic interneurons preferentially populate the lateral aspect of the striatum and mature earlier than late-born (after embryonic day 12.5) neurons, which normally reside in the medial part of the striatum. In the absence ofGbx2, early-born striatal cholinergic precursors display abnormal neurite outgrowth and increased complexity, and abnormally contribute to the medial part of the caudate–putamen, whereas late-born striatal cholinergic interneurons are mostly missing. Together, our data demonstrate thatGbx2is required for the development of striatal cholinergic interneurons, perhaps by regulating tangential migration of the striatal cholinergic precursors. |
| Databáze: | OpenAIRE |
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