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Volume 16, Number 23, Issue of December 1, 1996 pp. 7661-7669
Copyright ©1996 Society for Neuroscience

Neurotrophin-3 Is a Survival Factor In Vivo for Early Mouse Trigeminal Neurons

Received July 30, 1996; revised Sept. 10, 1996; accepted Sept. 18, 1996.

George A. Wilkinson¹, Isabel Fariñas¹, Carey Backus², Cathleen K. Yoshida¹, and Louis F. Reichardt²

¹ Department of Physiology and ² The Howard Hughes Medical Institute, University of California, San Francisco, San Francisco, California 94143

Mice lacking neurotrophin-3 (NT-3) have been shown previously to be born with severe sensory deficits. This study characterizes the developmental course of this deficit in the trigeminal sensory ganglion, which in NT-3 homozygous mutants contains only 35% of the normal number of neurons at birth. At embryonic day 10.5 (E10.5), normal numbers of neurons, as assessed by expression of neurofilament protein and of total cells, are present in the ganglia of mutant homozygotes. During the next 3 d (E10.5-E13.5), virtually all of the deficit develops, after which mutant animals retain only ~30% the normal number of neurons. Quantification of neuronal and neuronal precursor numbers in normal and mutant animals reveals that neurons are specifically depleted in the absence of NT-3. A deficiency in precursor proliferation is only seen after most of the neuronal deficit has developed. Numbers of apoptotic cells in the ganglia of mutant animals are elevated during this same interval, indicating that the neuronal deficit is caused, in large part, by increased cell death of embryonic neurons.

To determine sources of NT-3 in the trigeminal system, we examined the expression pattern of -galactosidase in mice, in which lacZ has replaced the NT-3 coding exon. E10.5-E11.5 embryos exhibit intense reporter expression throughout the mesenchyme and epithelia of the first branchial arch. -galactosidase expression in E13.5 embryos is largely confined to the oral epithelium and the mesenchyme underlying the skin. Throughout the E10.5-E13.5 interval, the trigeminal ganglion and its targets in the CNS do not express reporter activity.

We conclude that NT-3 acts principally as a peripherally derived survival factor for early trigeminal neurons.

Key words: neuronal development; neurotrophins; sensory neurons; apoptosis; mutant mouse

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