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Published online before print June 17, 2009, doi:10.1212/WNL.0b013e3181af3397)
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Received November 13, 2008
Accepted April 16, 2009

Layer-specific genes reveal a rudimentary laminar pattern in human nodular heterotopia

R. Garbelli PhD*, L. Rossini PhD, R. F. Moroni PhD, A. Watakabe PhD, T. Yamamori PhD, L. Tassi MD, M. Bramerio MD, G. L. Russo MD, C. Frassoni PhD, and R. Spreafico MD, PhD

From the Clinical Epileptology and Experimental Neurophysiology Unit (R.G., L.R., R.F.M., C.F., R.S.), Fondazione I.R.C.C.S., Istituto Neurologico "C. Besta," Milan, Italy; Division of Brain Biology (A.W., T.Y.), National Institute for Basic Biology, Okazaki, Japan; and Epilepsy Surgery Center "C. Munari" (L.T., G.L.R.), Department of Pathology (M.B.), Niguarda Hospital, Milan, Italy.


* To whom correspondence should be addressed. E-mail: garbelli.r{at}istituto-besta.it.

Objective: To define distinctive features of nodular heterotopia in specimens derived from drug-resistant patients with epilepsy by evaluating mRNA expression of three different layer-specific markers: Ror{beta}, Er81, and Nurr1.

Methods: We analyzed the expression profile of these genes, recognized as markers mainly expressed in layer IV for Ror{beta}, in layer V for Er81, and in layer VI for Nurr1, in surgical samples from 14 epileptic patients, using in situ hybridization. Six patients had subcortical nodular heterotopia and 8 patients were controls. The intrinsic organization of nodular formations and of the overlaying neocortex was assessed.

Results: In all patients, the 3 selected genes showed high cortical laminar specificity. In subcortical nodular heterotopia, the different gene expression profiles revealed a rudimentary laminar organization of the nodules. In the overlaying cortex, fewer cells expressed the 3 genes in the appropriate specific layer as compared to controls.

Conclusions: These data provide new insights into possible ontogenetic mechanisms of nodular heterotopia formation and show the potential role of layer-specific markers to elucidate the neuropathology of malformations of cortical development.


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R. J. Ferland and R. Guerrini
Nodular heterotopia is built upon layers
Neurology, September 8, 2009; 73(10): 742 - 743.
[Full Text] [PDF]


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