A role for Gsh1 in the developing striatum and olfactory bulb of Gsh2 mutant mice.

We have examined the role of the two closely related homeobox genes Gsh1 and Gsh2, in the development of the striatum and the olfactory bulb. These two genes are expressed in a partially overlapping pattern by ventricular zone progenitors of the ventral telencephalon. Gsh2 is expressed in both of the ganglionic eminences while Gsh1 is largely confined to the medial ganglionic eminence. Previous studies have shown that Gsh2(-/-) embryos suffer from an early misspecification of precursors in the lateral ganglionic eminence (LGE) leading to disruptions in striatal and olfactory bulb development. This molecular misspecification is present only in early precursor cells while at later stages the molecular identity of these cells appears to be normalized. Concomitant with this normalization, Gsh1 expression is notably expanded in the Gsh2(-/-) LGE. While no obvious defects in striatal or olfactory bulb development were detected in Gsh1(-/-) embryos, Gsh1/2 double homozygous mutants displayed more severe disruptions than were observed in the Gsh2 mutant alone. Accordingly, the molecular identity of LGE precursors in the double mutant is considerably more perturbed than in Gsh2 single mutants. These findings, therefore, demonstrate an important role for Gsh1 in the development of the striatum and olfactory bulb of Gsh2 mutant mice. In addition, our data indicate a role for Gsh genes in controlling the size of the LGE precursor pools, since decreasing copies of Gsh2 and Gsh1 alleles results in a notable decrease in precursor cell number, particularly in the subventricular zone.

[1]  J. Rubenstein,et al.  Gsh2 and Pax6 play complementary roles in dorsoventral patterning of the mammalian telencephalon. , 2001, Development.

[2]  G. Fishell,et al.  The Gsh2 homeodomain gene controls multiple aspects of telencephalic development. , 2000, Development.

[3]  P. Gruss,et al.  Pax6 Modulates the Dorsoventral Patterning of the Mammalian Telencephalon , 2000, The Journal of Neuroscience.

[4]  H. Toresson,et al.  Genetic control of dorsal-ventral identity in the telencephalon: opposing roles for Pax6 and Gsh2. , 2000, Development.

[5]  S. Anderson,et al.  Origin and Molecular Specification of Striatal Interneurons , 2000, The Journal of Neuroscience.

[6]  U. Dräger,et al.  A retinoic acid synthesizing enzyme in ventral retina and telencephalon of the embryonic mouse , 2000, Mechanisms of Development.

[7]  F. Guillemot,et al.  A role for neural determination genes in specifying the dorsoventral identity of telencephalic neurons. , 2000, Genes & development.

[8]  R. Grosschedl,et al.  Ebf1 controls early cell differentiation in the embryonic striatum. , 1999, Development.

[9]  S. Anderson,et al.  DLX‐1, DLX‐2, and DLX‐5 expression define distinct stages of basal forebrain differentiation , 1999, The Journal of comparative neurology.

[10]  S. Anderson,et al.  Differential origins of neocortical projection and local circuit neurons: role of Dlx genes in neocortical interneuronogenesis. , 1999, Cerebral cortex.

[11]  J. García-Verdugo,et al.  Young neurons from medial ganglionic eminence disperse in adult and embryonic brain , 1999, Nature Neuroscience.

[12]  H. Toresson,et al.  Retinoids are produced by glia in the lateral ganglionic eminence and regulate striatal neuron differentiation. , 1999, Development.

[13]  F. Guillemot,et al.  Mash1 regulates neurogenesis in the ventral telencephalon. , 1999, Development.

[14]  C. Walsh,et al.  Clonal mixing, clonal restriction, and specification of cell types in the developing rat olfactory bulb , 1999, The Journal of comparative neurology.

[15]  Richard Axel,et al.  An Olfactory Sensory Map Develops in the Absence of Normal Projection Neurons or GABAergic Interneurons , 1998, Neuron.

[16]  Garrett E. Alexander.  Basal ganglia , 1998 .

[17]  A. Björklund,et al.  Early specification of striatal projection neurons and interneuronal subtypes in the lateral and medial ganglionic eminence , 1998, Neuroscience.

[18]  S. Aizawa,et al.  Cooperation between Otx1 and Otx2 genes in developmental patterning of rostral brain , 1997, Mechanisms of Development.

[19]  S. Potter,et al.  Altered forebrain and hindbrain development in mice mutant for the Gsh-2 homeobox gene. , 1997, Developmental biology.

[20]  A. Simeone,et al.  Genetic control of brain morphogenesis through Otx gene dosage requirement. , 1997, Development.

[21]  S. Anderson,et al.  Mutations of the Homeobox Genes Dlx-1 and Dlx-2 Disrupt the Striatal Subventricular Zone and Differentiation of Late Born Striatal Neurons , 1997, Neuron.

[22]  B. Edgar,et al.  Developmental Control of Cell Cycle Regulators: A Fly's Perspective , 1996, Science.

[23]  S. Potter,et al.  Gsh‐1, an orphan Hox gene, is required for normal pituitary development. , 1996, The EMBO journal.

[24]  A. Björklund,et al.  Projection neurons in fetal striatal transplants are predominantly derived from the lateral ganglionic eminence , 1995, Neuroscience.

[25]  Gurparkash Singh,et al.  Gsh‐1: A novel murine homeobox gene expressed in the central nervous system , 1995, Developmental dynamics : an official publication of the American Association of Anatomists.

[26]  O. Isacson,et al.  The lateral ganglionic eminence is the origin of cells committed to striatal phenotypes: neural transplantation and developmental evidence , 1994, Brain Research.

[27]  L. Puelles,et al.  DLX-2, MASH-1, and MAP-2 expression and bromodeoxyuridine incorporation define molecularly distinct cell populations in the embryonic mouse forebrain , 1994, The Journal of neuroscience : the official journal of the Society for Neuroscience.

[28]  C. Lois,et al.  Long-distance neuronal migration in the adult mammalian brain. , 1994, Science.

[29]  J. Gerdes,et al.  The cell proliferation-associated antigen of antibody Ki-67: a very large, ubiquitous nuclear protein with numerous repeated elements, representing a new kind of cell cycle-maintaining proteins , 1993, The Journal of cell biology.

[30]  Maria B. Luskin,et al.  Restricted proliferation and migration of postnatally generated neurons derived from the forebrain subventricular zone , 1993, Neuron.

[31]  C. Gerfen.  The neostriatal mosaic: multiple levels of compartmental organization , 1992, Trends in Neurosciences.

[32]  A. Reiner,et al.  Immunohistochemical localization of DARPP-32 in striatal projection neurons and striatal interneurons: implications for the localization of D1-like dopamine receptors on different types of striatal neurons , 1991, Brain Research.

[33]  P. Greengard,et al.  Development of a dopamine- and cyclic adenosine 3':5'-monophosphate- regulated phosphoprotein (DARPP-32) in the prenatal rat central nervous system, and its relationship to the arrival of presumptive dopaminergic innervation , 1987, The Journal of neuroscience : the official journal of the Society for Neuroscience.

[34]  G. Fishell,et al.  Neuronal birthdate underlies the development of striatal compartments , 1987, Brain Research.

[35]  B. Kolb,et al.  The development of a patchy organization of the rat striatum. , 1986, Brain research.

[36]  C. Gerfen,et al.  The neostriatal mosaic: compartmental distribution of calcium-binding protein and parvalbumin in the basal ganglia of the rat and monkey. , 1985, Proceedings of the National Academy of Sciences of the United States of America.

[37]  M. Herkenham,et al.  Comparative development of striatal opiate receptors and dopamine revealed by autoradiography and histofluorescence , 1984, Brain Research.

[38]  A. Joyner,et al.  Engrailed, Wnt and Pax genes regulate midbrain--hindbrain development. , 1996, Trends in genetics : TIG.