Neuropediatrics 2009; 40(1): 6-14
DOI: 10.1055/s-0029-1224099
Original Article

© Georg Thieme Verlag KG Stuttgart · New York

POMT1-Associated Walker-Warburg Syndrome: A Disorder of Dendritic Development of Neocortical Neurons

M. Judaš 1 , G. Sedmak 1 , M. Radoš 1 , 2 , V. Sarnavka 3 , K. Fumić 4 , T. Willer 5 , C. Gross 6 , U. Hehr 6 , S. Strahl 5 , M. Ćuk 3 , I. Barić 3
  • 1Croatian Institute for Brain Research, School of Medicine, University of Zagreb, Zagreb, Croatia
  • 2Department of Radiology, Clinical Hospital Center Zagreb & School of Medicine, University of Zagreb, Zagreb, Croatia
  • 3Department of Pediatrics, Clinical Hospital Center Zagreb & School of Medicine, University of Zagreb, Zagreb, Croatia
  • 4Clinical Institute for Laboratory Diagnostics, Clinical Hospital Center Zagreb & School of Medicine, University of Zagreb, Zagreb, Croatia
  • 5Heidelberg Institute of Plant Science, Department V Cell Chemistry, Ruprecht-Karls-University Heidelberg, Germany
  • 6Center for Human Genetics, Regensburg, Germany
Further Information

Publication History

received 07.05.2008

accepted 17.04.2009

Publication Date:
28 July 2009 (online)

Abstract

We have analyzed the morphology and dendritic development of neocortical neurons in a 2.5-month-old infant with Walker-Warburg syndrome homozygotic for a novel POMT1 gene mutation, by Golgi methods. We found that pyramidal neurons frequently displayed abnormal (oblique, horizontal, or inverted) orientation. A novel finding of this study is that members of the same population of pyramidal neurons display different stages of development of their dendritic arborizations: some neurons had poorly developed dendrites and thus resembled pyramidal neurons of the late fetal cortex; for some neurons, the level of differentiation corresponded to that in the newborn cortex; finally, some neurons had quite elaborate dendritic trees as expected for the cortex of 2.5-month-old infant. In addition, apical dendrites of many pyramidal neurons were conspiciously bent to one side, irrespective to the general orientation of the pyramidal neuron. These findings suggest that Walker-Warburg lissencephaly is characterized by two hitherto unnoticed pathogenetic changes in the cerebral cortex: (a) heterochronic decoupling of dendritic maturation within the same neuronal population (with some members significantly lagging behind the normal maturational schedule) and (b) anisotropically distorted shaping of dendritic trees, probably caused by patchy displacement of molecular guidance cues for dendrites in the malformed cortex.

References

Correspondence

Prof. M. Judaš

Department of Neuroscience

Croatian Institute for Brain Research

School of Medicine

University of Zagreb

Šalata 12

10000 Zagreb

Croatia

Phone: +385/1/45 96 801

Fax: +385/1/45 96 942

Email: mjudas@hiim.hr