Genetic Interactions between Doublecortin and Doublecortin-like Kinase in Neuronal Migration and Axon Outgrowth

@article{Deuel2006GeneticIB,
  title={Genetic Interactions between Doublecortin and Doublecortin-like Kinase in Neuronal Migration and Axon Outgrowth},
  author={Thomas A.S Deuel and Judy S. H. Liu and Joseph C. Corbo and Seung-Yun Yoo and Lucy Balian Rorke-Adams and Christopher A. Walsh},
  journal={Neuron},
  year={2006},
  volume={49},
  pages={41-53}
}
Although mutations in the human doublecortin gene (DCX) cause profound defects in cortical neuronal migration, a genetic deletion of Dcx in mice produces a milder defect. A second locus, doublecortin-like kinase (Dclk), encodes a protein with similar "doublecortin domains" and microtubule stabilization properties that may compensate for Dcx. Here, we generate a mouse with a Dclk mutation that causes no obvious migrational abnormalities but show that mice mutant for both Dcx and Dclk demonstrate… Expand
Different Doublecortin (DCX) Patient Alleles Show Distinct Phenotypes in Cultured Neurons
TLDR
Several patient DCX alleles are characterized using a gain-of-function dendrite growth assay in cultured rat neurons in combination with the determination of molecular binding activities and subcellular localization in non-neuronal and neuronal cells and it is suggested that distinct Dcx alleles caused dysfunction by different mechanisms. Expand
Both Doublecortin and Doublecortin-Like Kinase Play a Role in Cortical Interneuron Migration
TLDR
The importance of these genes in interneuron migration was confirmed by the finding that the cortices of D cx, Dclk, and Dcx/Dclk mutant mice contained a reduced number of such cells in the cortex and their distribution was different compared with wild-type controls, suggesting that DCX and DCLK have distinct roles in cortical interneurons migration. Expand
A critical and previously unsuspected role for doublecortin at the neuromuscular junction in mouse and human
TLDR
The identified abnormal and denervated NMJs in a muscle biopsy from a 16-year-old female patient with SBH, showing both profound presynaptic and postsynaptic morphological defects point to a critical role of doublecortin in the formation of the NMJ. Expand
Doublecortin (DCX) Mediates Endocytosis of Neurofascin Independently of Microtubule Binding
TLDR
DCX can modulate the surface distribution of neurofascin in developing cultured rat neurons and thereby the relative extent of accumulation between the axon initial segment and soma and dendrites, and it is proposed that DCX acts as an endocytic adaptor for neurofASCin to fine-tune its surface distribution during neuronal development. Expand
Doublecortin (Dcx) Family Proteins Regulate Filamentous Actin Structure in Developing Neurons
TLDR
The phenotype of Dcx/Doublecortin-like kinase 1 deficiency is consistent with actin defect, as these axons are selectively deficient in axon guidance, but not elongation. Expand
Mice lacking doublecortin and doublecortin-like kinase 2 display altered hippocampal neuronal maturation and spontaneous seizures
TLDR
The data suggest that hippocampal dysmaturation and insufficient receptive field for inhibitory input may underlie the epilepsy in lissencephaly, and suggest potential therapeutic strategies for controlling epilepsy in these patients. Expand
Understanding doublecortin-like kinase gene function through transgenesis
TLDR
Transgenic mice with over-expression of either CARP or a constitutively active form of DCLK-short, called δC-DCLK -short, in the brain are generated and the phenotypes of these transgenic mice are described at different functional levels, such as the genetic, network and behavioural level. Expand
A dominant dendrite phenotype caused by the disease-associated G253D mutation in doublecortin (DCX) is not due to its endocytosis defect
TLDR
A known function for doublecortin, namely, increasing dendrite growth in cultured neurons, is investigated, and it is found that the DCX-ALPA andDCX-G253D mutants yield distinct d endocytosis phenotypes. Expand
Evidence that Doublecortin Is Dispensable for the Development of Adult Born Neurons in Mice
TLDR
The present data indicate that DCX is dispensable for the development of new neurons in adult mice, and it is shown that micro (mi) RNA-mediated retroviral knockdown of DCX does not alter morphological maturation of adult born dentate granule cells or migration ofnew neurons in either adult neurogenic niche. Expand
The doublecortin and doublecortin-like kinase 1 genes cooperate in murine hippocampal development.
TLDR
It is shown that the two genes display overlapping expression patterns in developing mouse hippocampus, which suggests these genes are partially functionally redundant in the formation of the murine hippocampus. Expand
...
1
2
3
4
5
...

References

SHOWING 1-10 OF 63 REFERENCES
Doublecortin Association with Actin Filaments Is Regulated by Neurabin II*
TLDR
It is demonstrated that Dcx co-sediments with actin filaments (F-actin), and using light and electron microscopy and spin down assays, it is shown that D cx induces bundling and cross-linking of microtubules and F- actin in vitro. Expand
DCAMKL1 Encodes a Protein Kinase with Homology to Doublecortin that Regulates Microtubule Polymerization
TLDR
It is shown that DCAMKL1 is expressed throughout the CNS and PNS in migrating neuronal populations and overlaps in its expression with DCX and microtubules, and the two proteins form a potentially mutually regulatory network linking calcium signaling andmicrotubule dynamics. Expand
Doublecortin Is a Microtubule-Associated Protein and Is Expressed Widely by Migrating Neurons
TLDR
It is demonstrated that DCX is expressed in migrating neurons throughout the central and peripheral nervous system during embryonic and postnatal development and likely directs neuronal migration by regulating the organization and stability of microtubules. Expand
Doublecortin Is Required in Mice for Lamination of the Hippocampus But Not the Neocortex
TLDR
Behavioral tests show defects in context and cued conditioned fear tests, suggesting that deficits in hippocampal learning accompany the abnormal cytoarchitecture. Expand
Patient Mutations in Doublecortin Define a Repeated Tubulin-binding Domain*
TLDR
Evidence is provided that the interaction of DCX with microtubules is dependent upon this novel repeated tubulin-binding motif, and representative patient missense mutations lead to impaired polymerization both in vitro and in vivo as well as impaired microtubule stabilization. Expand
The DCX-domain tandems of doublecortin and doublecortin-like kinase
TLDR
A solution structure of the N-terminal DCX domain of human doublecortin and the equivalent domain from human DCLK are reported, which show a stable, ubiquitin-like tertiary fold with distinct structural similarities to GTPase-binding domains. Expand
High expression of doublecortin and KIAA0369 protein in fetal brain suggests their specific role in neuronal migration.
TLDR
Western blotting demonstrated that both DC and KI are specific to the nervous system and are abundant during the fetal period, around 20 gestational weeks in humans and embryonic days 17 to 20 in rats, suggesting that DC andKI participate in a common signaling pathway regulating neuronal migration. Expand
RNAi reveals doublecortin is required for radial migration in rat neocortex
TLDR
In utero RNAi can be effectively used to study the specific cellular roles of DCX in neocortical development and to produce an animal model of double cortex syndrome. Expand
Doublecortin Is a Developmentally Regulated, Microtubule-Associated Protein Expressed in Migrating and Differentiating Neurons
TLDR
It is shown that Doublecortin is expressed in the brain throughout the period of corticogenesis in migrating and differentiating neurons, and Immunohistochemical studies show its localization in the soma and leading processes of tangentially migrating neuron, and a strong axonal labeling is observed in differentiating neuron. Expand
Cyclin-Dependent Kinase 5-Deficient Mice Demonstrate Novel Developmental Arrest in Cerebral Cortex
TLDR
A model in which the cdk5−/− defect blocks cortical development at a heretofore undescribed intermediate stage, after the splitting of the preplate, but before the migration of the full complement of cortical neurons is proposed. Expand
...
1
2
3
4
5
...