Mutations in the BMP pathway in mice support the existence of two molecular classes of holoprosencephaly.
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.
Fernandes
Marie
M
Department of Neuroscience, Albert Einstein College of Medicine, Bronx, NY 10461, USA.
Gutin
Grigoriy
G
Alcorn
Heather
H
McConnell
Susan K
SK
Hébert
Jean M
JM
D000818:Animals; D052005:Bone Morphogenetic Protein Receptors, Type I / Q000172:deficiency / Q000235:genetics / Q000378:metabolism; D019485:Bone Morphogenetic Proteins / Q000235:genetics / Q000378:metabolism*; D001921:Brain / Q000196:embryology / Q000378:metabolism; D004622:Embryo, Mammalian / Q000196:embryology / Q000378:metabolism; D005260:Female; D018507:Gene Expression Regulation, Developmental; D053823:Hedgehog Proteins / Q000235:genetics / Q000378:metabolism; D016142:Holoprosencephaly / Q000196:embryology / Q000235:genetics / Q000378:metabolism*; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D009154:Mutation / Q000235:genetics*; D010641:Phenotype; D015398:Signal Transduction
D019485:Bone Morphogenetic Proteins; D053823:Hedgehog Proteins; C465570:Shh protein, mouse; D052005:Bone Morphogenetic Protein Receptors, Type I