Depletion of Inositol Polyphosphate 4-Phosphatase II Suppresses Callosal Axon Formation in the Developing Mice.
The corpus callosum is a bundle of nerve fibers that connects the two cerebral hemispheres and is essential for coordinated transmission of information between them. Disruption of early stages of callosal development can cause agenesis of the corpus callosum (AgCC), including both complete and partial callosal absence, causing mild to severe cognitive impairment. Despite extensive studies, the etiology of AgCC remains to be clarified due to the complicated mechanism involved in generating AgCC. The biological function of PI3K signaling including phosphatidylinositol-3,4,5-trisphosphate is well established in diverse biochemical processes including axon and dendrite morphogenesis, but the function of the closely related phosphatidylinositol-3,4,-bisphosphate (PI(3,4)P2) signaling, particularly in the nervous system, is largely unknown. Here, we provide the first report on the role of inositol polyphosphate 4-phosphatase II (INPP4B), a PI(3,4)P2 metabolizing 4-phosphatase in the regulation of callosal axon formation. Depleting INPP4B by in utero electroporation suppressed medially directed callosal axon formation. Moreover, depletion of INPP4B significantly attenuated formation of Satb2-positive pyramidal neurons and axon polarization in cortical neurons during cortical development. Taken together, these data suggest that INPP4B plays a role in the regulating callosal axon formation by controlling axon polarization and the Satb2-positive pyramidal neuron population. Dysregulation of INPP4B during cortical development may be implicated in the generation of partial AgCC.
Department of Pharmacology, College of Medicine, Hallym University, Chunchon 200-702, Korea.
Liting
L
Ji
Department of Pharmacology, College of Medicine, Hallym University, Chunchon 200-702, Korea.
Nam-Ho
NH
Kim
Department of Pharmacology, College of Medicine, Hallym University, Chunchon 200-702, Korea.|Institute of Natural Medicine, Hallym University, Chunchon 200-702, Korea.
Sung-Oh
SO
Huh
Institute of Natural Medicine, Hallym University, Chunchon 200-702, Korea.
Hae Jin
HJ
Rhee
D061085:Agenesis of Corpus Callosum / Q000235:genetics*; D000818:Animals; D000831:Animals, Newborn; D001369:Axons / Q000648:ultrastructure*; D003337:Corpus Callosum / Q000254:growth & development*; D005260:Female; D018507:Gene Expression Regulation, Developmental; D036961:Matrix Attachment Region Binding Proteins / Q000378:metabolism; D051379:Mice; D010744:Phosphoric Monoester Hydrolases / Q000172:deficiency*; D011247:Pregnancy; D017966:Pyramidal Cells / Q000378:metabolism; D014157:Transcription Factors / Q000378:metabolism
D036961:Matrix Attachment Region Binding Proteins; C501473:SATB2 protein, mouse; D014157:Transcription Factors; D010744:Phosphoric Monoester Hydrolases; C053153:phosphatidylinositol-3,4-bisphosphate 4-phosphatase
agenesis of the corpus callosum; axon polarization; callosal axon; cortical development; inositol polyphosphate 4-phosphatase II; phosphatidylinositol-3,4,-bisphosphate