The Journal of Neuroscience, April 1, 1999, 19(7):2601-2608
Sonic Hedgehog Promotes Neuronal Differentiation of Murine Spinal
Cord Precursors and Collaborates with Neurotrophin 3 to Induce
Islet-1
Renée
Dutton3,
Toshiya
Yamada2,
Ann
Turnley1,
Perry F.
Bartlett1, and
Mark
Murphy3
1 Walter and Eliza Hall Institute of Medical Research,
Royal Melbourne Hospital, Parkville, Victoria, Australia 3050, 2 Centre for Cellular and Molecular Biology, University of
Queensland, Brisbane, Queensland, Australia 4067, and
3 Department of Anatomy and Cell Biology, The University of
Melbourne, Parkville, Victoria, Australia 3052
Sonic hedgehog (Shh) is strongly implicated in the development of
ventral structures in the nervous system. Addition of Sonic hedgehog
protein to chick spinal cord explants induces floor plate and
motoneuron development. Whether Shh acts directly to induce these cell
types or whether their induction is mediated by additional factors is
unknown. To further investigate the role of Shh in spinal neuron
development, we have used low-density cultures of murine spinal cord
precursor cells. Shh stimulated neuronal differentiation; however, it
did not increase the proportion of neurons expressing the first
postmitotic motoneuron marker Islet-1. Moreover, Shh did induce Islet-1
expression in neural tube explants, suggesting that it acts in
combination with neural tube factors to induce motoneurons. Another
factor implicated in motoneuron development is neurotrophin 3 (NT3),
and when assayed in isolated precursor cultures, it had no effect on
Islet-1 expression. However, the combination of N-terminal Shh and NT3
induced Islet-1 expression in the majority of neurons in low-density
cultures of caudal intermediate neural plate. Furthermore, in explant
cultures, Shh-mediated Islet-1 expression was blocked by an anti-NT3
antibody. Previous studies have shown expression of NT3 in the region
of motoneuron differentiation and that spinal fusimotor neurons are
lost in NT3 knock-out animals. Taken together, these findings suggest
that Shh can act directly on spinal cord precursors to promote neuronal
differentiation, but induction of Islet-1 expression is regulated by
factors additional to Shh, including NT3.
Key words:
sonic hedgehog; neurotrophin 3; Islet-1; motoneurons; spinal cord; neural tube
Copyright © 1999 Society for Neuroscience 0270-6474/99/1972601-08$05.00/0
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