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SDF1 regulates leading process branching and speed of migrating interneurons.

ABSTRACT: Cell migration is required for normal embryonic development, yet how cells navigate complex paths while integrating multiple guidance cues remains poorly understood. During brain development, interneurons migrate from the ventral ganglionic eminence to the cerebral cortex within several migratory streams. They must exit these streams to invade the cortical plate. While SDF1 (stromal cell-derived factor-1) signaling is necessary for normal interneuron stream migration, how they switch from tangential stream migration to invade the cortical plate is unknown. Here, we demonstrate that SDF1 signaling reduces interneuron branching frequency by reducing cAMP levels via a G(i) signaling pathway using an in vitro mouse explant system, resulting in the maintenance of stream migration. Blocking SDF1 signaling or increasing branching frequency results in stream exit and cortical plate invasion in mouse brain slices. These data support a novel model to understand how migrating interneurons switch from tangential migration to invade the cortical plate in which reducing SDF signaling increases leading process branching and slows the migration rate, permitting migrating interneurons to sense cortically directed guidance cues.

SUBMITTER: Lysko DE

PROVIDER: S-EPMC3038431 | biostudies-literature | 2011 Feb

REPOSITORIES: biostudies-literature

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SDF1 regulates leading process branching and speed of migrating interneurons.

Lysko Daniel E DE Putt Mary M Golden Jeffrey A JA

The Journal of neuroscience : the official journal of the Society for Neuroscience 20110201 5

Cell migration is required for normal embryonic development, yet how cells navigate complex paths while integrating multiple guidance cues remains poorly understood. During brain development, interneurons migrate from the ventral ganglionic eminence to the cerebral cortex within several migratory streams. They must exit these streams to invade the cortical plate. While SDF1 (stromal cell-derived factor-1) signaling is necessary for normal interneuron stream migration, how they switch from tangen ...[more]

PMID: 21289183

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Project description:Key pointsTau mislocalization to dendritic spines and associated postsynaptic deficits are mediated through different and non-overlapping phosphorylation sites. Tau mislocalization to dendritic spines depends upon the phosphorylation of either Ser396 or Ser404 in the C-terminus. Postsynaptic dysfunction instead depends upon the phosphorylation of at least one of five residues in the proline-rich region of tau. The blockade of both glycogen synthetase kinase 3β and cyclin-dependent kinase 5 is required to prevent P301L-induced tau mislocalization to dendritic spines, supporting redundant pathways that control tau mislocalization to spines.AbstractTau protein consists of an N-terminal projection domain, a microtubule-binding domain and a C-terminal domain. In neurodegenerative diseases, including Alzheimer's disease and frontotemporal dementia, the hyperphosphorylation of tau changes its shape, binding partners and resulting function. An early consequence of tau phosphorylation by proline-directed kinases is postsynaptic dysfunction associated with the mislocalization of tau to dendritic spines. The specific phosphorylation sites leading to these abnormalities have not been elucidated. Here, using imaging and electrophysiological techniques to study cultured rat hippocampal neurons, we show that postsynaptic dysfunction results from a sequential process involving differential phosphorylation in the N-terminal and C-terminal domains. First, tau mislocalizes to dendritic spines, in a manner that depends upon the phosphorylation of either Ser396 or Ser404 in the C-terminal domain. The blockade of both glycogen synthetase kinase 3β and cyclin-dependent kinase 5 prevents tau mislocalization to dendritic spines. Second, a reduction of functional AMPA receptors depends upon the phosphorylation of at least one of five residues (Ser202, Thr205, Thr212, Thr217 and Thr231) in the proline-rich region of the N-terminal domain. This is the first report of differential phosphorylation in distinct tau domains governing separate, but linked, steps leading to synaptic dysfunction.

Dataset Information

SDF1 regulates leading process branching and speed of migrating interneurons.

Publications

SDF1 regulates leading process branching and speed of migrating interneurons.

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