Development, Vol 125, Issue 15 2759-2770, Copyright © 1998 by Company of Biologists

JOURNAL ARTICLES

Gli2 is required for induction of floor plate and adjacent cells, but not most ventral neurons in the mouse central nervous system

MP Matise, DJ Epstein, HL Park, KA Platt and AL Joyner
Developmental Genetics Program and Howard Hughes Medical Institute, and Department of Cell Biology and Physiology and Neuroscience, NYU Medical Center, New York, NY 10016, USA.

Induction of the floor plate at the ventral midline of the neural tube is one of the earliest events in the establishment of dorsoventral (d/v) polarity in the vertebrate central nervous system (CNS). The secreted molecule, Sonic hedgehog, has been shown to be both necessary and sufficient for this induction. In vertebrates, several downstream components of this signalling pathway have been identified, including members of the Gli transcription factor family. In this study, we have examined d/v patterning of the CNS in Gli2 mouse mutants. We have found that the floor plate throughout the midbrain, hindbrain and spinal cord does not form in Gli2 homozygotes. Despite this, motoneurons and ventral interneurons form in their normal d/v positions at 9.5 to 12.5 days postcoitum (dpc). However, cells that are generated in the region flanking the floor plate, including dopaminergic and serotonergic neurons, were greatly reduced in number or absent in Gli2 homozygous embryos. These results suggest that early signals derived from the notochord can be sufficient for establishing the basic d/v domains of cell differentiation in the ventral spinal cord and hindbrain. Interestingly, the notochord in Gli2 mutants does not regress ventrally after 10.5 dpc, as in normal embryos. Finally, the spinal cord of Gli1/Gli2 zinc-finger-deletion double homozygous mutants appeared similar to Gli2 homozygotes, indicating that neither gene is required downstream of Shh for the early development of ventral cell fates outside the ventral midline.
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				A. Borycki, B Brunk, S Tajbakhsh, M Buckingham, C Chiang, and C. Emerson Sonic hedgehog controls epaxial muscle determination through Myf5 activation Development, January 9, 1999; 126(18): 4053 - 4063. [Abstract] [PDF]

				L Sussel, O Marin, S Kimura, and J. Rubenstein Loss of Nkx2.1 homeobox gene function results in a ventral to dorsal molecular respecification within the basal telencephalon: evidence for a transformation of the pallidum into the striatum Development, January 8, 1999; 126(15): 3359 - 3370. [Abstract] [PDF]

				T Theil, G Alvarez-Bolado, A Walter, and U Ruther Gli3 is required for Emx gene expression during dorsal telencephalon development Development, January 8, 1999; 126(16): 3561 - 3571. [Abstract] [PDF]

				M. Matise, M Lustig, T Sakurai, M Grumet, and A. Joyner Ventral midline cells are required for the local control of commissural axon guidance in the mouse spinal cord Development, January 8, 1999; 126(16): 3649 - 3659. [Abstract] [PDF]

				D Arendt and K Nubler-Jung Comparison of early nerve cord development in insects and vertebrates Development, January 6, 1999; 126(11): 2309 - 2325. [Abstract] [PDF]

				K. Lewis, G Drossopoulou, I. Paton, D. Morrice, K. Robertson, D. Burt, P. Ingham, and C Tickle Expression of ptc and gli genes in talpid3 suggests bifurcation in Shh pathway Development, January 6, 1999; 126(11): 2397 - 2407. [Abstract] [PDF]

				A Ruiz i Altaba Gli proteins encode context-dependent positive and negative functions: implications for development and disease Development, January 6, 1999; 126(14): 3205 - 3216. [Abstract] [PDF]

				F Muller, B Chang, S Albert, N Fischer, L Tora, and U Strahle Intronic enhancers control expression of zebrafish sonic hedgehog in floor plate and notochord Development, January 5, 1999; 126(10): 2103 - 2116. [Abstract] [PDF]

				D. Epstein, A. McMahon, and A. Joyner Regionalization of Sonic hedgehog transcription along the anteroposterior axis of the mouse central nervous system is regulated by Hnf3-dependent and -independent mechanisms Development, January 1, 1999; 126(2): 281 - 292. [Abstract] [PDF]

				Y. Koyabu, K. Nakata, K. Mizugishi, J. Aruga, and K. Mikoshiba Physical and Functional Interactions between Zic and Gli Proteins J. Biol. Chem., March 2, 2001; 276(10): 6889 - 6892. [Abstract] [Full Text] [PDF]

				M. Nilsson, A. B. Unden, D. Krause, U. Malmqwist, K. Raza, P. G. Zaphiropoulos, and R. Toftgard Induction of basal cell carcinomas and trichoepitheliomas in mice overexpressing GLI-1 PNAS, March 28, 2000; 97(7): 3438 - 3443. [Abstract] [Full Text] [PDF]