The development of the cerebral cortex relies on the controlled division of neural stem and progenitor cells. The requirement for precise spatiotemporal control of proliferation and cell fate places a high demand on the cell division machinery, and defective cell division can cause microcephaly and other brain malformations. Cell-extrinsic and -intrinsic factors govern the capacity of cortical progenitors to produce large numbers of neurons and glia within a short developmental time window. In particular, ion channels shape the intrinsic biophysical properties of precursor cells and neurons and control their membrane potential throughout the cell cycle. We found that hyperpolarization-activated cyclic nucleotide-gated cation (HCN) channel subunits are expressed in mouse, rat, and human neural progenitors. Loss of HCN channel function in rat neural stem cells impaired their proliferation by affecting the cell-cycle progression, causing G1 accumulation and dysregulation of genes associated with human microcephaly. Transgene-mediated, dominant-negative loss of HCN channel function in the embryonic mouse telencephalon resulted in pronounced microcephaly. Together, our findings suggest a role for HCN channel subunits as a part of a ...Continue Reading
Immunocytochemical and physiological characterization of a population of cultured human neural precursors
Persistently modified h-channels after complex febrile seizures convert the seizure-induced enhancement of inhibition to hyperexcitability
Differential and age-dependent expression of hyperpolarization-activated, cyclic nucleotide-gated cation channel isoforms 1-4 suggests evolving roles in the developing rat hippocampus
Early development of voltage-gated ion currents and firing properties in neurons of the mouse cerebral cortex
The hyperpolarization-activated HCN1 channel is important for motor learning and neuronal integration by cerebellar Purkinje cells
The hyperpolarization-activated channel HCN4 is required for the generation of pacemaker action potentials in the embryonic heart
Conditional transgenic suppression of M channels in mouse brain reveals functions in neuronal excitability, resonance and behavior
Distinct profiles of REST interactions with its target genes at different stages of neuronal development
Pyramidal neurons of upper cortical layers generated by NEX-positive progenitor cells in the subventricular zone
Quantitative analysis and subcellular distribution of mRNA and protein expression of the hyperpolarization-activated cyclic nucleotide-gated channels throughout development in rat hippocampus.
Regulated expression of HCN channels and cAMP levels shape the properties of the h current in developing rat hippocampus
Characterization of excitability and voltage-gated ion channels of neural progenitor cells in rat hippocampus.
Noninvasive imaging of endogenous neural stem cell mobilization in vivo using positron emission tomography.
Effects of hyperpolarization-activated cyclic nucleotide-gated (HCN) channel blockers on the proliferation and cell cycle progression of embryonic stem cells
Neuron-restrictive silencer factor-mediated hyperpolarization-activated cyclic nucleotide gated channelopathy in experimental temporal lobe epilepsy.
Is ZD7288 a selective blocker of hyperpolarization-activated cyclic nucleotide-gated channel currents?
Microcephaly gene links trithorax and REST/NRSF to control neural stem cell proliferation and differentiation
Microarray-Based Comparisons of Ion Channel Expression Patterns: Human Keratinocytes to Reprogrammed hiPSCs to Differentiated Neuronal and Cardiac Progeny
cAMP promotes the differentiation of neural progenitor cells in vitro via modulation of voltage-gated calcium channels
Deficiency of asparagine synthetase causes congenital microcephaly and a progressive form of encephalopathy
The transcription factor NRSF contributes to epileptogenesis by selective repression of a subset of target genes
Cardiac arrhythmia induced by genetic silencing of 'funny' (f) channels is rescued by GIRK4 inactivation
Age-dependent loss of parvalbumin-expressing hippocampal interneurons in mice deficient in CHL1, a mental retardation and schizophrenia susceptibility gene
Adult Stem Cells
Adult stem cells reside in unique niches that provide vital cues for their survival, self-renewal, and differentiation. They hold great promise for use in tissue repair and regeneration as a novel therapeutic strategies. Here is the latest research.