Loss of adenylyl cyclase I activity disrupts patterning of mouse somatosensory cortex

Abstract

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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Figure 1: Genetic maps of proximal mouse chromosome 11.
Figure 2: Adenylyl cyclase activity in two-week wild-type and brl mutant mice.
Figure 3: Mutational analysis of Adcy1 in brl mutant mice.
Figure 4: Digitized images of layer IV of SI cortex from seven-month Adcy1 (a) and Adcy8 (b) knockout mice.

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Acknowledgements

We thank A. Blackadar, B. Cusack and K. Furue for technical assistance, and H. Lehrach and F.B. Palmer for support. This work has been supported by the Medical Research Council of Canada (grant MT-12941).

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Correspondence to Paul E. Neumann.

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Abdel-Majid, R., Leong, W., Schalkwyk, L. et al. Loss of adenylyl cyclase I activity disrupts patterning of mouse somatosensory cortex. Nat Genet 19, 289–291 (1998). https://doi.org/10.1038/980

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