title: Functional synergy between cholecystokinin receptors CCKAR and CCKBR in mammalian brain development.
abstract: Cholecystokinin (CCK), a peptide hormone and one of the most abundant neuropeptides in vertebrate brain, mediates its actions via two G-protein coupled receptors, CCKAR and CCKBR, respectively active in peripheral organs and the central nervous system. Here, we demonstrate that the CCK receptors have a dynamic and largely reciprocal expression in embryonic and postnatal brain. Using compound homozygous mutant mice lacking the activity of both CCK receptors, we uncover their additive, functionally synergistic effects in brain development and demonstrate that CCK receptor loss leads to abnormalities of cortical development, including defects in the formation of the midline and corpus callosum, and cortical interneuron migration. Using comparative transcriptome analysis of embryonic neocortex, we define the molecular mechanisms underlying these defects. Thus we demonstrate a developmental, hitherto unappreciated, role of the two CCK receptors in mammalian neocortical development.
authors: Department of Neurosurgery, Yale School of Medicine, New Haven, Connecticut, United States of America.
authors: Sayoko
authors: S
authors: Nishimura
authors: Yale Program on Neurogenetics, Yale School of Medicine, New Haven, Connecticut, United States of America; Department of Genetics, Yale School of Medicine, New Haven, Connecticut, United States of America; Yale Center for Genome Analysis, Yale School of Medicine, New Haven, Connecticut, United States of America.
authors: Kaya
authors: K
authors: Bilgüvar
authors: Department of Neurosurgery, Yale School of Medicine, New Haven, Connecticut, United States of America.
authors: Keiko
authors: K
authors: Ishigame
authors: Department of Neurobiology, Yale School of Medicine, New Haven, Connecticut, United States of America.
authors: Nenad
authors: N
authors: Sestan
authors: Department of Neurosurgery, Yale School of Medicine, New Haven, Connecticut, United States of America; Yale Program on Neurogenetics, Yale School of Medicine, New Haven, Connecticut, United States of America; Department of Genetics, Yale School of Medicine, New Haven, Connecticut, United States of America; Department of Neurobiology, Yale School of Medicine, New Haven, Connecticut, United States of America.
authors: Murat
authors: M
authors: Günel
authors: Department of Neurosurgery, Yale School of Medicine, New Haven, Connecticut, United States of America; Yale Program on Neurogenetics, Yale School of Medicine, New Haven, Connecticut, United States of America; Department of Neurobiology, Yale School of Medicine, New Haven, Connecticut, United States of America.
authors: Angeliki
authors: A
authors: Louvi
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D055419:Bone Morphogenetic Protein 7 / Q000235:genetics / Q000378:metabolism; D002465:Cell Movement; D054377:Chemokine CXCL12 / Q000235:genetics / Q000378:metabolism; D002766:Cholecystokinin / Q000378:metabolism*; D003337:Corpus Callosum / Q000166:cytology / Q000254:growth & development / Q000378:metabolism; D004622:Embryo, Mammalian; D020869:Gene Expression Profiling; D018507:Gene Expression Regulation, Developmental; D006720:Homozygote; D006801:Humans; D007395:Interneurons / Q000166:cytology / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D020644:Midline Thalamic Nuclei / Q000166:cytology / Q000254:growth & development / Q000378:metabolism; D009154:Mutation; D019579:Neocortex / Q000166:cytology / Q000254:growth & development / Q000378:metabolism*; D039943:Neuropilin-2 / Q000235:genetics / Q000378:metabolism; D043886:Receptor, Cholecystokinin A / Q000235:genetics* / Q000378:metabolism; D043887:Receptor, Cholecystokinin B / Q000235:genetics* / Q000378:metabolism; D016194:Receptors, N-Methyl-D-Aspartate / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction; D059467:Transcriptome
chemical_list: D055419:Bone Morphogenetic Protein 7; D054377:Chemokine CXCL12; C515256:Cxcl12 protein, mouse; D039943:Neuropilin-2; D043886:Receptor, Cholecystokinin A; D043887:Receptor, Cholecystokinin B; D016194:Receptors, N-Methyl-D-Aspartate; C525820:bmp7 protein, mouse; D002766:Cholecystokinin