Mutations in the BMP pathway in mice support the existence of two molecular classes of holoprosencephaly
Author:
Fernandes Marie1, Gutin Grigoriy1, Alcorn Heather2, McConnell Susan K.3, Hébert Jean M.1
Affiliation:
1. Departments of Neuroscience and Molecular Genetics, Albert Einstein College of Medicine, Bronx, NY 10461, USA. 2. Developmental Biology Program, Sloan-Kettering Institute, New York, NY 10021,USA. 3. Department of Biological Sciences, Stanford University, Stanford, CA,USA.
Abstract
Holoprosencephaly (HPE) is a devastating forebrain abnormality with a range of morphological defects characterized by loss of midline tissue. In the telencephalon, the embryonic precursor of the cerebral hemispheres,specialized cell types form a midline that separates the hemispheres. In the present study, deletion of the BMP receptor genes, Bmpr1b and Bmpr1a, in the mouse telencephalon results in a loss of all dorsal midline cell types without affecting the specification of cortical and ventral precursors. In the holoprosencephalic Shh-/- mutant, by contrast, ventral patterning is disrupted, whereas the dorsal midline initially forms. This suggests that two separate developmental mechanisms can underlie the ontogeny of HPE. The Bmpr1a;Bmpr1b mutant provides a model for a subclass of HPE in humans: midline inter-hemispheric HPE.
Publisher
The Company of Biologists
Subject
Developmental Biology,Molecular Biology
Reference51 articles.
1. Anderson, R. M., Lawrence, A. R., Stottmann, R. W., Bachiller,D. and Klingensmith, J. (2002). Chordin and noggin promote organizing centers of forebrain development in the mouse. Development129,4975-4987. 2. Aoto, K., Nishimura, T., Eto, K. and Motoyama, J.(2002). Mouse GLI3 regulates Fgf8 expression and apoptosis in the developing neural tube, face, and limb bud. Dev. Biol.251,320-332. 3. Barkovich, A. J. and Quint, D. J. (1993). Middle interhemispheric fusion: an unusual variant of holoprosencephaly. AJNR Am. J. Neuroradiol.14,431-440. 4. Blackshear, P. J., Graves, J. P., Stumpo, D. J., Cobos, I.,Rubenstein, J. L. and Zeldin, D. C. (2003). Graded phenotypic response to partial and complete deficiency of a brain-specific transcript variant of the winged helix transcription factor RFX4. Development130,4539-4552. 5. Brown, L. Y., Odent, S., David, V., Blayau, M., Dubourg, C.,Apacik, C., Delgado, M. A., Hall, B. D., Reynolds, J. F., Sommer, A. et al. (2001). Holoprosencephaly due to mutations in ZIC2:alanine tract expansion mutations may be caused by parental somatic recombination. Hum. Mol. Genet.10,791-796.
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