Dixdc1 Is a Critical Regulator of DISC1 and Embryonic Cortical Development Journal Articles

abstract

• The psychiatric illness risk gene Disrupted in Schizophrenia-1 (DISC1) plays an important role in brain development; however, it is unclear how DISC1 is regulated during cortical development. Here, we report that DISC1 is regulated during embryonic neural progenitor proliferation and neuronal migration through an interaction with DIX domain containing-1 (Dixdc1), the third mammalian gene discovered to contain a Disheveled-Axin (DIX) domain. We determined that Dixdc1 functionally interacts with DISC1 to regulate neural progenitor proliferation by co-modulating Wnt-GSK3beta/beta-catenin signaling. However, DISC1 and Dixdc1 do not regulate migration via this pathway. During neuronal migration, we discovered that phosphorylation of Dixdc1 by cyclin-dependent kinase 5 (Cdk5) facilitates its interaction with the DISC1-binding partner Ndel1. Furthermore, Dixdc1 phosphorylation and its interaction with DISC1/Ndel1 in vivo is required for neuronal migration. Together, these data reveal that Dixdc1 integrates DISC1 into Wnt-GSK3beta/beta-catenin-dependent and -independent signaling pathways during cortical development and further delineate how DISC1 contributes to neuropsychiatric disorders.

authors

• Singh, Karun
• Ge, Xuecai
• Mao, Yingwei
• Drane, Laurel
• Meletis, Konstantinos
• Samuels, Benjamin A
• Tsai, Li-Huei

status

• published 

publication date

• July 2010

has subject area

• 1109 Neurosciences (FoR)
• 1701 Psychology (FoR)
• 1702 Cognitive Sciences (FoR)
• Animals (MeSH)
• Animals, Newborn (MeSH)
• Bromodeoxyuridine (MeSH)
• Cell Cycle Proteins (MeSH)
• Cell Movement (MeSH)
• Cell Proliferation (MeSH)
• Cells, Cultured (MeSH)
• Cerebral Cortex (MeSH)
• Electroporation (MeSH)
• Embryo, Mammalian (MeSH)
• Female (MeSH)
• Gene Expression Regulation, Developmental (MeSH)
• Green Fluorescent Proteins (MeSH)
• Humans (MeSH)
• Intracellular Signaling Peptides and Proteins (MeSH)
• Luminescent Proteins (MeSH)
• Mice (MeSH)
• Microfilament Proteins (MeSH)
• Microtubule-Associated Proteins (MeSH)
• Nerve Tissue Proteins (MeSH)
• Neurology & Neurosurgery (Science Metrix)
• Neurons (MeSH)
• Pregnancy (MeSH)
• Protein Binding (MeSH)
• RNA Interference (MeSH)
• Signal Transduction (MeSH)
• Stem Cells (MeSH)
• Transfection (MeSH)
• Wnt Proteins (MeSH)

published in

• Neuron  Journal

keywords

• Animals
• Animals, Newborn
• Bromodeoxyuridine
• Cell Cycle Proteins
• Cell Movement
• Cell Proliferation
• Cells, Cultured
• Cerebral Cortex
• Electroporation
• Embryo, Mammalian
• Female
• Gene Expression Regulation, Developmental
• Green Fluorescent Proteins
• Humans
• Intracellular Signaling Peptides and Proteins
• Luminescent Proteins
• Mice
• Microfilament Proteins
• Microtubule-Associated Proteins
• Nerve Tissue Proteins
• Neurons
• Pregnancy
• Protein Binding
• RNA Interference
• Signal Transduction
• Stem Cells
• Transfection
• Wnt Proteins

Digital Object Identifier (DOI)

• 10.1016/j.neuron.2010.06.002

start page

• 33

end page

• 48

volume

• 67

issue

• 1