The homeodomain protein vax1 is required for axon guidance and major tract formation in the developing forebrain.
The homeodomain protein Vax1 is expressed in a highly circumscribed set of cells at the ventral anterior midline of the embryonic CNS. These cells populate the choroid fissure of the optic disk, the body of the optic stalk and nerve, the optic chiasm and ventral diencephalon, and the anterior midline zones that abut developing commissural tracts. We have generated mutant mice that lack Vax1. In these mice (1) the optic disks fail to close, leading to coloboma and loss of the eye-nerve boundary; (2) optic nerve glia fail to associate with and appear to repulse ingrowing retinal axons, resulting in a fascicle of axons that are completely segregated from optic nerve astrocytes; (3) retinal axons fail to penetrate the brain in significant numbers and fail to form an optic chiasm; and (4) axons in multiple commissural tracts of the anterior CNS, including the corpus callosum and the hippocampal and anterior commissures, fail to cross the midline. These axon guidance defects do not result from the death of normally Vax1(+) midline cells but, instead, correlate with markedly diminished expression of attractive guidance cues in these cells. Vax1 therefore regulates the guidance properties of a set of anterior midline cells that orchestrate axon trajectories in the developing mammalian forebrain.
Bertuzzi
S
S
Molecular Neurobiology Laboratory, The Salk Institute for Biological Studies, La Jolla, California 92037, USA.
Hindges
R
R
Mui
S H
SH
O'Leary
D D
DD
Lemke
G
G
D000015:Abnormalities, Multiple / Q000196:embryology / Q000235:genetics*; D061085:Agenesis of Corpus Callosum; D000818:Animals; D000831:Animals, Newborn; D001369:Axons / Q000502:physiology*; D003103:Coloboma / Q000196:embryology / Q000235:genetics; D003337:Corpus Callosum / Q000378:metabolism; D005314:Embryonic and Fetal Development / Q000235:genetics; D017353:Gene Deletion; D005801:Genes, Homeobox; D005804:Genes, Lethal; D018398:Homeodomain Proteins / Q000235:genetics / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009024:Morphogenesis / Q000235:genetics; D009479:Neuropeptides / Q000235:genetics / Q000502:physiology*; D009897:Optic Chiasm / Q000002:abnormalities / Q000196:embryology; D009898:Optic Disk / Q000002:abnormalities / Q000196:embryology; D009900:Optic Nerve / Q000002:abnormalities / Q000196:embryology; D016548:Prosencephalon / Q000196:embryology*; D012165:Retinal Ganglion Cells / Q000648:ultrastructure
D018398:Homeodomain Proteins; D009479:Neuropeptides; C485177:Vax1 protein, mouse