Teruyuki Tanaka - Academia.edu (original) (raw)
Papers by Teruyuki Tanaka
Nature Neuroscience, 2006
PloS one, 2018
Mutations in the Cyclin-dependent kinase-like 5 (CDKL5) gene cause severe neurodevelopmental diso... more Mutations in the Cyclin-dependent kinase-like 5 (CDKL5) gene cause severe neurodevelopmental disorders. Recently we have generated Cdkl5 KO mice by targeting exon 2 on the C57BL/6N background, and demonstrated postsynaptic overaccumulation of GluN2B-containing N-methyl-D-aspartate (NMDA) receptors in the hippocampus. In the current study, we subjected the Cdkl5 KO mice to a battery of comprehensive behavioral tests, aiming to reveal the effects of loss of CDKL5 in a whole perspective of motor, emotional, social, and cognition/memory functions, and to identify its undetermined roles. The neurological screen, rotarod, hot plate, prepulse inhibition, light/dark transition, open field, elevated plus maze, Porsolt forced swim, tail suspension, one-chamber and three-chamber social interaction, 24-h home cage monitoring, contextual and cued fear conditioning, Barnes maze, and T-maze tests were applied on adult Cdkl5 -/Y and +/Y mice. Cdkl5 -/Y mice showed a mild alteration in the gait. Ana...
Neurobiology of disease, 2017
Mutations in the Cyclin-dependent kinase-like 5 (CDKL5) gene cause severe neurodevelopmental diso... more Mutations in the Cyclin-dependent kinase-like 5 (CDKL5) gene cause severe neurodevelopmental disorders accompanied by intractable epilepsies, i.e. West syndrome or atypical Rett syndrome. Here we report generation of the Cdkl5 knockout mouse and show that CDKL5 controls postsynaptic localization of GluN2B-containing N-methyl-d-aspartate (NMDA) receptors in the hippocampus and regulates seizure susceptibility. Cdkl5 -/Y mice showed normal sensitivity to kainic acid; however, they displayed significant hyperexcitability to NMDA. In concordance with this result, electrophysiological analysis in the hippocampal CA1 region disclosed an increased ratio of NMDA/α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor-mediated excitatory postsynaptic currents (EPSCs) and a significantly larger decay time constant of NMDA receptor-mediated EPSCs (NMDA-EPSCs) as well as a stronger inhibition of the NMDA-EPSCs by the GluN2B-selective antagonist ifenprodil in Cdkl5 -/Y mice. Subcell...
Curr Opin Pediatr, 2000
The identification of the specific genes responsible for several childhood neurologic disorders h... more The identification of the specific genes responsible for several childhood neurologic disorders has provided a framework with which to understand key development stages in human brain development. Common genetic disorders of brain development include septo-optic dysplasia, schizencephaly, holoprosencephaly, periventricular heterotopia, lissencephaly, and Joubert syndrome. For each of these disorders, a critical step in brain development is interrupted. The identification of the responsible genes is providing scientists a window into the key modulators of brain development, and providing clinicians the opportunity to offer genetic testing to individual patients and their families.
Transgenic Research, May 1, 2004
The centrosome plays diverse roles throughout the cellular mitotic cycle and in post-mitotic cell... more The centrosome plays diverse roles throughout the cellular mitotic cycle and in post-mitotic cells. Analysis of centrosome position and dynamics in living murine cells has been limited due to a lack of adequate reporters and currently requires either cell fixation/immunostaining or transfection with centrosome reporters. Here we describe the generation and characterization of a transgenic mouse line that constitutively expresses green fluorescent protein-labeled Centrin-2 (GFP-CETN2). The phenotype of the mouse is indistinguishable from wild-type and it displays a single pair of fluorescent centrioles in cells of every organ and time point examined. This model will be helpful for visualizing the centrosome in multiple experimental conditions.
Nihon yakurigaku zasshi. Folia pharmacologica Japonica, 2015
The Journal of neuroscience : the official journal of the Society for Neuroscience, 2003
Humans with heterozygous inactivating mutations of the Lis1 gene display type I lissencephaly, a ... more Humans with heterozygous inactivating mutations of the Lis1 gene display type I lissencephaly, a severe form of cortical dysplasia hypothesized to result from abnormal neuronal migration. Previously we reported the construction of an allelic series of the Lis1 gene in mice to analyze the effects of graded reduction of LIS1 protein on the pathogenesis of this disorder and demonstrated a cell autonomous defect in neuronal migration (Hirotsune et al., 1998). Here we report the systematic examination of the consequences of dosage reduction of LIS1 on neocortical development using wild-type, null heterozygous (45% LIS1 protein), and compound null/hypomorphic (35% LIS1 protein) mice. The development of the preplate, Cajal-Retzius cells, and the radial glial scaffold appeared unaffected by LIS1 levels. However, a dose-dependent morphologic change in disorganization of the subplate was noted. LIS1 dose-dependent defects in neuronal migration were found in vivo and in vitro. The position and...
Open biology, Jan 17, 2013
Microtubules (MTs) are essential for neuronal morphogenesis in the developing brain. The MT cytos... more Microtubules (MTs) are essential for neuronal morphogenesis in the developing brain. The MT cytoskeleton provides physical support to shape the fine structure of neuronal processes. MT-based motors play important roles in nucleokinesis, process formation and retraction. Regulation of MT stability downstream of extracellular cues is proposed to be critical for axonogenesis. Axons and dendrites exhibit different patterns of MT organization, underlying the divergent functions of these processes. Centrosomal positioning has drawn the attention of researchers because it is a major clue to understanding neuronal MT organization. In this review, we focus on how recent advances in live imaging have revealed the dynamics of MT organization and centrosome positioning during neural development.
Handbook of clinical neurology, 2008
Neuron, Jan 5, 2006
The potential role of doublecortin (Dcx), encoding a microtubule-associated protein, in brain dev... more The potential role of doublecortin (Dcx), encoding a microtubule-associated protein, in brain development has remained controversial. Humans with mutations show profound alterations in cortical lamination, whereas in mouse, RNAi-mediated knockdown but not germline knockout shows abnormal positioning of cortical neurons. Here, we report that the doublecortin-like kinase (Dclk) gene functions in a partially redundant pathway with Dcx in the formation of axonal projections across the midline and migration of cortical neurons. Dosage-dependent genetic effects were observed in both interhemispheric connectivity and migration of cortically and subcortically derived neurons. Surprisingly, RNAi-mediated knockdown of either gene results in similar migration defects. These results indicate the Dcx microtubule-associated protein family is required for proper neuronal migration and axonal wiring.
No to hattatsu. Brain and development, 2002
We report a 12-year-old boy with idiopathic torsion dystonia. Blepharospasm appeared at the age o... more We report a 12-year-old boy with idiopathic torsion dystonia. Blepharospasm appeared at the age of 10, followed by truncal hypertonia and progressive scoliosis after 1 year. He had bizarre involuntary movement of his limbs upon waking, which was initially misinterpreted as a psychogenic reaction. Routine neurological examinations revealed no abnormality. Treatment with diazepam, bacrophen, 1-dopa, and clonazepam, led to only short time improvement of symptoms. At the age of 14, his symptoms gradually improved in natural course. At present he is 15 years old, and capable of normal daily activities. His clinical course was not typical of idiopathic torsion dystonia and very rare in children.
Development (Cambridge, England), Jan 15, 2015
Muscle satellite cells are indispensable for muscle regeneration, but the functional diversity of... more Muscle satellite cells are indispensable for muscle regeneration, but the functional diversity of their daughter cells is unknown. Here, we show that many Pax7 + MyoD − cells locate both beneath and outside the basal lamina during myofiber maturation. A large majority of these Pax7 + MyoD − cells are not self-renewed satellite cells, but have different potentials for both proliferation and differentiation from Pax7 + MyoD + myoblasts (classical daughter cells), and are specifically marked by expression of the doublecortin (Dcx) gene. Transplantation and lineage-tracing experiments demonstrated that Dcx-expressing cells originate from quiescent satellite cells and that the microenvironment induces Dcx in myoblasts. Expression of Dcx seems to be necessary for myofiber maturation because Dcx-deficient mice exhibited impaired myofiber maturation resulting from a decrease in the number of myonuclei. Furthermore, in vitro and in vivo studies suggest that one function of Dcx in myogenic cells is acceleration of cell motility. These results indicate that Dcx is a new marker for the Pax7 + MyoD − subpopulation, which contributes to myofiber maturation during muscle regeneration.
Transgenic Research, 2000
The centrosome plays diverse roles throughout the cellular mitotic cycle and in post-mitotic cell... more The centrosome plays diverse roles throughout the cellular mitotic cycle and in post-mitotic cells. Analysis of centrosome position and dynamics in living murine cells has been limited due to a lack of adequate reporters and currently requires either cell fixation/immunostaining or transfection with centrosome reporters. Here we describe the generation and characterization of a transgenic mouse line that constitutively expresses green fluorescent protein-labeled Centrin-2 (GFP-CETN2). The phenotype of the mouse is indistinguishable from wild-type and it displays a single pair of fluorescent centrioles in cells of every organ and time point examined. This model will be helpful for visualizing the centrosome in multiple experimental conditions.
Neuroscience Research, 2010
Nature Communications, 2013
Dendritic morphogenesis and formation of synapses at appropriate dendritic locations are essentia... more Dendritic morphogenesis and formation of synapses at appropriate dendritic locations are essential for the establishment of proper neuronal connectivity. Recent imaging studies provide evidence for stabilization of dynamic distal branches of dendrites by the addition of new synapses. However, molecules involved in both dendritic growth and suppression of synapse maturation remain to be identified. Here we report two distinct functions of doublecortin-like kinases, chimeric proteins containing both a microtubule-binding domain and a kinase domain in postmitotic neurons. First, doublecortin-like kinases localize to the distal dendrites and promote their growth by enhancing microtubule bundling. Second, doublecortin-like kinases suppress maturation of synapses through multiple pathways, including reduction of PSD-95 by the kinase domain and suppression of spine structural maturation by the microtubule-binding domain. Thus, doublecortin-like kinases are critical regulators of dendritic development by means of their specific targeting to the distal dendrites, and their local control of dendritic growth and synapse maturation.
Molecular and Cellular Neuroscience, 2006
In comparison with other migratory cells, neurons exhibit a unique, highly polarized morphology a... more In comparison with other migratory cells, neurons exhibit a unique, highly polarized morphology and a distinctive pattern of movement. This migration consists of a repeating of three distinct phases: neurite outgrowth, movement of the centrosome into the leading process, and translocation of the nucleus towards the centrosome. The direction of movement is under the control of extracellular guidance cues, but mechanisms by which these determine neuronal polarity, centrosome position, and neuronal movement are not well understood. We found that in primary olfactory bulb neuronal precursors, Slit-mediated repolarization consisted of growth of a new process from the previous trailing edge, then reorientation of the centrosome followed by nuclear translocation in the reverse direction. Inhibition of cell polarity factors GSK3B or PKCZ resulted in impaired centrosome reorientation and process stabilization. Our findings suggest that activation of cell polarity signaling and positioning of the centrosome ahead of the nucleus are important steps in repolarization in response to guidance cues.
Epilepsia, 2000
Recent progress in surgical intervention for mcdically refractory epilepsy has hclped to shed lig... more Recent progress in surgical intervention for mcdically refractory epilepsy has hclped to shed light on more complex epileptogcnic problems in children and infants. Surgical treatment increasingly is being used in pediatric patients, but the indications for surgery in this age group have not been well dcfincd. The developing child with a seizure disordcr has sevcral problems that are dilferent from adults, such as neural plasticity, dclctcrious effccts of seizures on developmental status, and spontaneous resolution of cpilcpsy. The critical age for irreversiblc brain dysfunction and the timing of surgery arc the main issues for thc treatment of children. Thus, carlier surgical intervention is generally recommended to prevent further detrimental seizure effccts, but we still do not know the optimal age. Until the establishment of guidelines for pediatric cpilcpsy surgery, surgical indications should be determined by the prognosis and the presence of a rescctahlc cpilcptogcnic rocus, which in turn are bascd on the localization of the epileptic focus, seizure frequency, scvcrity, and cognitive function of each case, rather than just the patient's age.
Current Opinion in Pediatrics, 2000
The identification of the specific genes responsible for several childhood neurologic disorders h... more The identification of the specific genes responsible for several childhood neurologic disorders has provided a framework with which to understand key development stages in human brain development. Common genetic disorders of brain development include septo-optic dysplasia, schizencephaly, holoprosencephaly, periventricular heterotopia, lissencephaly, and Joubert syndrome. For each of these disorders, a critical step in brain development is interrupted. The identification of the responsible genes is providing scientists a window into the key modulators of brain development, and providing clinicians the opportunity to offer genetic testing to individual patients and their families.
Nature Neuroscience, 2006
PloS one, 2018
Mutations in the Cyclin-dependent kinase-like 5 (CDKL5) gene cause severe neurodevelopmental diso... more Mutations in the Cyclin-dependent kinase-like 5 (CDKL5) gene cause severe neurodevelopmental disorders. Recently we have generated Cdkl5 KO mice by targeting exon 2 on the C57BL/6N background, and demonstrated postsynaptic overaccumulation of GluN2B-containing N-methyl-D-aspartate (NMDA) receptors in the hippocampus. In the current study, we subjected the Cdkl5 KO mice to a battery of comprehensive behavioral tests, aiming to reveal the effects of loss of CDKL5 in a whole perspective of motor, emotional, social, and cognition/memory functions, and to identify its undetermined roles. The neurological screen, rotarod, hot plate, prepulse inhibition, light/dark transition, open field, elevated plus maze, Porsolt forced swim, tail suspension, one-chamber and three-chamber social interaction, 24-h home cage monitoring, contextual and cued fear conditioning, Barnes maze, and T-maze tests were applied on adult Cdkl5 -/Y and +/Y mice. Cdkl5 -/Y mice showed a mild alteration in the gait. Ana...
Neurobiology of disease, 2017
Mutations in the Cyclin-dependent kinase-like 5 (CDKL5) gene cause severe neurodevelopmental diso... more Mutations in the Cyclin-dependent kinase-like 5 (CDKL5) gene cause severe neurodevelopmental disorders accompanied by intractable epilepsies, i.e. West syndrome or atypical Rett syndrome. Here we report generation of the Cdkl5 knockout mouse and show that CDKL5 controls postsynaptic localization of GluN2B-containing N-methyl-d-aspartate (NMDA) receptors in the hippocampus and regulates seizure susceptibility. Cdkl5 -/Y mice showed normal sensitivity to kainic acid; however, they displayed significant hyperexcitability to NMDA. In concordance with this result, electrophysiological analysis in the hippocampal CA1 region disclosed an increased ratio of NMDA/α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor-mediated excitatory postsynaptic currents (EPSCs) and a significantly larger decay time constant of NMDA receptor-mediated EPSCs (NMDA-EPSCs) as well as a stronger inhibition of the NMDA-EPSCs by the GluN2B-selective antagonist ifenprodil in Cdkl5 -/Y mice. Subcell...
Curr Opin Pediatr, 2000
The identification of the specific genes responsible for several childhood neurologic disorders h... more The identification of the specific genes responsible for several childhood neurologic disorders has provided a framework with which to understand key development stages in human brain development. Common genetic disorders of brain development include septo-optic dysplasia, schizencephaly, holoprosencephaly, periventricular heterotopia, lissencephaly, and Joubert syndrome. For each of these disorders, a critical step in brain development is interrupted. The identification of the responsible genes is providing scientists a window into the key modulators of brain development, and providing clinicians the opportunity to offer genetic testing to individual patients and their families.
Transgenic Research, May 1, 2004
The centrosome plays diverse roles throughout the cellular mitotic cycle and in post-mitotic cell... more The centrosome plays diverse roles throughout the cellular mitotic cycle and in post-mitotic cells. Analysis of centrosome position and dynamics in living murine cells has been limited due to a lack of adequate reporters and currently requires either cell fixation/immunostaining or transfection with centrosome reporters. Here we describe the generation and characterization of a transgenic mouse line that constitutively expresses green fluorescent protein-labeled Centrin-2 (GFP-CETN2). The phenotype of the mouse is indistinguishable from wild-type and it displays a single pair of fluorescent centrioles in cells of every organ and time point examined. This model will be helpful for visualizing the centrosome in multiple experimental conditions.
Nihon yakurigaku zasshi. Folia pharmacologica Japonica, 2015
The Journal of neuroscience : the official journal of the Society for Neuroscience, 2003
Humans with heterozygous inactivating mutations of the Lis1 gene display type I lissencephaly, a ... more Humans with heterozygous inactivating mutations of the Lis1 gene display type I lissencephaly, a severe form of cortical dysplasia hypothesized to result from abnormal neuronal migration. Previously we reported the construction of an allelic series of the Lis1 gene in mice to analyze the effects of graded reduction of LIS1 protein on the pathogenesis of this disorder and demonstrated a cell autonomous defect in neuronal migration (Hirotsune et al., 1998). Here we report the systematic examination of the consequences of dosage reduction of LIS1 on neocortical development using wild-type, null heterozygous (45% LIS1 protein), and compound null/hypomorphic (35% LIS1 protein) mice. The development of the preplate, Cajal-Retzius cells, and the radial glial scaffold appeared unaffected by LIS1 levels. However, a dose-dependent morphologic change in disorganization of the subplate was noted. LIS1 dose-dependent defects in neuronal migration were found in vivo and in vitro. The position and...
Open biology, Jan 17, 2013
Microtubules (MTs) are essential for neuronal morphogenesis in the developing brain. The MT cytos... more Microtubules (MTs) are essential for neuronal morphogenesis in the developing brain. The MT cytoskeleton provides physical support to shape the fine structure of neuronal processes. MT-based motors play important roles in nucleokinesis, process formation and retraction. Regulation of MT stability downstream of extracellular cues is proposed to be critical for axonogenesis. Axons and dendrites exhibit different patterns of MT organization, underlying the divergent functions of these processes. Centrosomal positioning has drawn the attention of researchers because it is a major clue to understanding neuronal MT organization. In this review, we focus on how recent advances in live imaging have revealed the dynamics of MT organization and centrosome positioning during neural development.
Handbook of clinical neurology, 2008
Neuron, Jan 5, 2006
The potential role of doublecortin (Dcx), encoding a microtubule-associated protein, in brain dev... more The potential role of doublecortin (Dcx), encoding a microtubule-associated protein, in brain development has remained controversial. Humans with mutations show profound alterations in cortical lamination, whereas in mouse, RNAi-mediated knockdown but not germline knockout shows abnormal positioning of cortical neurons. Here, we report that the doublecortin-like kinase (Dclk) gene functions in a partially redundant pathway with Dcx in the formation of axonal projections across the midline and migration of cortical neurons. Dosage-dependent genetic effects were observed in both interhemispheric connectivity and migration of cortically and subcortically derived neurons. Surprisingly, RNAi-mediated knockdown of either gene results in similar migration defects. These results indicate the Dcx microtubule-associated protein family is required for proper neuronal migration and axonal wiring.
No to hattatsu. Brain and development, 2002
We report a 12-year-old boy with idiopathic torsion dystonia. Blepharospasm appeared at the age o... more We report a 12-year-old boy with idiopathic torsion dystonia. Blepharospasm appeared at the age of 10, followed by truncal hypertonia and progressive scoliosis after 1 year. He had bizarre involuntary movement of his limbs upon waking, which was initially misinterpreted as a psychogenic reaction. Routine neurological examinations revealed no abnormality. Treatment with diazepam, bacrophen, 1-dopa, and clonazepam, led to only short time improvement of symptoms. At the age of 14, his symptoms gradually improved in natural course. At present he is 15 years old, and capable of normal daily activities. His clinical course was not typical of idiopathic torsion dystonia and very rare in children.
Development (Cambridge, England), Jan 15, 2015
Muscle satellite cells are indispensable for muscle regeneration, but the functional diversity of... more Muscle satellite cells are indispensable for muscle regeneration, but the functional diversity of their daughter cells is unknown. Here, we show that many Pax7 + MyoD − cells locate both beneath and outside the basal lamina during myofiber maturation. A large majority of these Pax7 + MyoD − cells are not self-renewed satellite cells, but have different potentials for both proliferation and differentiation from Pax7 + MyoD + myoblasts (classical daughter cells), and are specifically marked by expression of the doublecortin (Dcx) gene. Transplantation and lineage-tracing experiments demonstrated that Dcx-expressing cells originate from quiescent satellite cells and that the microenvironment induces Dcx in myoblasts. Expression of Dcx seems to be necessary for myofiber maturation because Dcx-deficient mice exhibited impaired myofiber maturation resulting from a decrease in the number of myonuclei. Furthermore, in vitro and in vivo studies suggest that one function of Dcx in myogenic cells is acceleration of cell motility. These results indicate that Dcx is a new marker for the Pax7 + MyoD − subpopulation, which contributes to myofiber maturation during muscle regeneration.
Transgenic Research, 2000
The centrosome plays diverse roles throughout the cellular mitotic cycle and in post-mitotic cell... more The centrosome plays diverse roles throughout the cellular mitotic cycle and in post-mitotic cells. Analysis of centrosome position and dynamics in living murine cells has been limited due to a lack of adequate reporters and currently requires either cell fixation/immunostaining or transfection with centrosome reporters. Here we describe the generation and characterization of a transgenic mouse line that constitutively expresses green fluorescent protein-labeled Centrin-2 (GFP-CETN2). The phenotype of the mouse is indistinguishable from wild-type and it displays a single pair of fluorescent centrioles in cells of every organ and time point examined. This model will be helpful for visualizing the centrosome in multiple experimental conditions.
Neuroscience Research, 2010
Nature Communications, 2013
Dendritic morphogenesis and formation of synapses at appropriate dendritic locations are essentia... more Dendritic morphogenesis and formation of synapses at appropriate dendritic locations are essential for the establishment of proper neuronal connectivity. Recent imaging studies provide evidence for stabilization of dynamic distal branches of dendrites by the addition of new synapses. However, molecules involved in both dendritic growth and suppression of synapse maturation remain to be identified. Here we report two distinct functions of doublecortin-like kinases, chimeric proteins containing both a microtubule-binding domain and a kinase domain in postmitotic neurons. First, doublecortin-like kinases localize to the distal dendrites and promote their growth by enhancing microtubule bundling. Second, doublecortin-like kinases suppress maturation of synapses through multiple pathways, including reduction of PSD-95 by the kinase domain and suppression of spine structural maturation by the microtubule-binding domain. Thus, doublecortin-like kinases are critical regulators of dendritic development by means of their specific targeting to the distal dendrites, and their local control of dendritic growth and synapse maturation.
Molecular and Cellular Neuroscience, 2006
In comparison with other migratory cells, neurons exhibit a unique, highly polarized morphology a... more In comparison with other migratory cells, neurons exhibit a unique, highly polarized morphology and a distinctive pattern of movement. This migration consists of a repeating of three distinct phases: neurite outgrowth, movement of the centrosome into the leading process, and translocation of the nucleus towards the centrosome. The direction of movement is under the control of extracellular guidance cues, but mechanisms by which these determine neuronal polarity, centrosome position, and neuronal movement are not well understood. We found that in primary olfactory bulb neuronal precursors, Slit-mediated repolarization consisted of growth of a new process from the previous trailing edge, then reorientation of the centrosome followed by nuclear translocation in the reverse direction. Inhibition of cell polarity factors GSK3B or PKCZ resulted in impaired centrosome reorientation and process stabilization. Our findings suggest that activation of cell polarity signaling and positioning of the centrosome ahead of the nucleus are important steps in repolarization in response to guidance cues.
Epilepsia, 2000
Recent progress in surgical intervention for mcdically refractory epilepsy has hclped to shed lig... more Recent progress in surgical intervention for mcdically refractory epilepsy has hclped to shed light on more complex epileptogcnic problems in children and infants. Surgical treatment increasingly is being used in pediatric patients, but the indications for surgery in this age group have not been well dcfincd. The developing child with a seizure disordcr has sevcral problems that are dilferent from adults, such as neural plasticity, dclctcrious effccts of seizures on developmental status, and spontaneous resolution of cpilcpsy. The critical age for irreversiblc brain dysfunction and the timing of surgery arc the main issues for thc treatment of children. Thus, carlier surgical intervention is generally recommended to prevent further detrimental seizure effccts, but we still do not know the optimal age. Until the establishment of guidelines for pediatric cpilcpsy surgery, surgical indications should be determined by the prognosis and the presence of a rescctahlc cpilcptogcnic rocus, which in turn are bascd on the localization of the epileptic focus, seizure frequency, scvcrity, and cognitive function of each case, rather than just the patient's age.
Current Opinion in Pediatrics, 2000
The identification of the specific genes responsible for several childhood neurologic disorders h... more The identification of the specific genes responsible for several childhood neurologic disorders has provided a framework with which to understand key development stages in human brain development. Common genetic disorders of brain development include septo-optic dysplasia, schizencephaly, holoprosencephaly, periventricular heterotopia, lissencephaly, and Joubert syndrome. For each of these disorders, a critical step in brain development is interrupted. The identification of the responsible genes is providing scientists a window into the key modulators of brain development, and providing clinicians the opportunity to offer genetic testing to individual patients and their families.