Nature Genetics
19, 289 - 291 (1998)
doi:10.1038/980
Loss of adenylyl cyclase I activity disrupts patterning of mouse somatosensory
cortexRaja M. Abdel-Majid1, Wey L. Leong2, 3, Leonard C. Schalkwyk4, Donald S. Smallman3, Scott T. Wong5, Daniel R. Storm5, Alan Fine6, Melanie J. Dobson7, Duane L. Guernsey3
& Paul E. Neumann1, 31
Department of Anatomy & Neurobiology, Faculty of
Medicine, Dalhousie University, Halifax, Nova Scotia,
Canada B3H 4H7. 2
Department of Surgery, Faculty of Medicine, Dalhousie
University, Halifax, Nova Scotia, Canada B3H 4H7. 3
Department of Pathology, Faculty of Medicine, Dalhousie
University, Halifax, Nova Scotia, Canada B3H 4H7. 4
Max-Planck-Institut für Molekulare Genetik,
Abteilung Lehrach, Berlin-Dahlem, Germany.
5
Department of Pharmacology, University of Washington,
Seattle, Washington, USA. R.M.A. and
W.L.L. contributed equally to this work. 6
Department of Physiology & Biophysics, Faculty
of Medicine, Dalhousie University, Halifax, Nova Scotia,
Canada B3H 4H7. 7
Department of Biochemistry, Faculty of Medicine, Dalhousie
University, Halifax, Nova Scotia, Canada B3H 4H7.
Correspondence should be addressed to Paul E. Neumann neumannp@tupdean1.med.dal.ca.The somatosensory (SI) cortex of mice displays a patterned, nonuniform
distribution of neurons in layer IV called the 'barrelfield' (
ref. 1). Thalamocortical afferents (TCAs) that terminate in layer
IV are segregated such that each barrel, a readily visible cylindrical array
of neurons surrounding a cell-sparse center, represents a distinct receptive
field. TCA arbors are confined to the barrel hollow and synapse on barrel-wall
neurons whose dendrites are oriented toward the center of the barrel2. Mice homozygous for the barrelless (brl) mutation, which
occurred spontaneously in ICR stock at Université de Lausanne (Switzerland),
fail to develop this patterned distribution of neurons, but still display
normal topological organization of the SI cortex3. Despite the
absence of barrels and the overlapping zones of TCA arborization, the size
of individual whisker representations, as judged by 2-deoxyglucose uptake,
is similar to that of wild-type mice. We identified adenylyl cyclase type
I (Adcy1) as the gene disrupted in brl mutant mice by fine mapping
of proximal chromosome 11, enzyme assay, mutation analysis and examination
of mice homozygous for a targeted disruption of Adcy1. These results
provide the first evidence for involvement of cAMP signalling pathways in
pattern formation of the brain.
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