Advertisement
JOURNAL ARTICLES
Genetic control of dorsal-ventral identity in the telencephalon: opposing roles for Pax6 and Gsh2
H. Toresson, S.S. Potter, K. Campbell
Development 2000 127: 4361-4371;

Summary

We have examined the genetic mechanisms that regulate dorsal-ventral identity in the embryonic mouse telencephalon and, in particular, the specification of progenitors in the cerebral cortex and striatum. The respective roles of Pax6 and Gsh2 in cortical and striatal development were studied in single and double loss-of-function mouse mutants. Gsh2 gene function was found to be essential to maintain the molecular identity of early striatal progenitors and in its absence the ventral telencephalic regulatory genes Mash1 and Dlx are lost from most of the striatal germinal zone. In their place, the dorsal regulators, Pax6, neurogenin 1 and neurogenin 2 are found ectopically. Conversely, Pax6 is required to maintain the correct molecular identity of cortical progenitors. In its absence, neurogenins are lost from the cortical germinal zone and Gsh2, Mash1 and Dlx genes are found ectopically. These reciprocal alterations in cortical and striatal progenitor specification lead to the abnormal development of the cortex and striatum observed in Pax6 (small eye) and Gsh2 mutants, respectively. In support of this, double homozygous mutants for Pax6 and Gsh2 exhibit significant improvements in both cortical and striatal development compared with their respective single mutants. Taken together, these results demonstrate that Pax6 and Gsh2 govern cortical and striatal development by regulating genetically opposing programs that control the expression of each other as well as the regionally expressed developmental regulators Mash1, the neurogenins and Dlx genes in telencephalic progenitors.

REFERENCES

    1. Anderson S. A.,
    2. Eisenstat D. D.,
    3. Shi L.,
    4. Rubenstein J. L.
    (1997) Interneuron migration from basal forebrain to neocortex: dependence on Dlx genes. Science 278, 474–476
    OpenUrlAbstract/FREE Full Text
    1. Anderson S. A.,
    2. Qui M.,
    3. Bulfone A.,
    4. Eisenstat D. D.,
    5. Meneses J.,
    6. Pedersen R.,
    7. Rubenstein J. L. R.
    (1997) Mutations of the homeobox gene Dlx-1 and Dlx-2 disrupt the striatal subventricular zone and differentiation of late born striatal neurons. Neuron 19, 27–37
    OpenUrlCrossRefPubMedWeb of Science
    1. Briata P.,
    2. Di Blas E.,
    3. Gulisano M.,
    4. Mallamaci A.,
    5. Iannone R.,
    6. Boncinelli E.,
    7. Corte G.
    (1996) EMX1 homeoprotein is expressed in cell nuclei of the developing cerebral cortex and in the axons of the olfactory sensory neurons. Mech Dev 57, 169–180
    OpenUrlCrossRefPubMedWeb of Science
    1. Briscoe J.,
    2. Sussel L.,
    3. Serup P.,
    4. Hartigan-O'Connor D.,
    5. Jessell T. M.,
    6. Rubenstein J. L.,
    7. Ericson J.
    (1999). Homeobox gene Nkx2.2 and specification of neuronal identity by graded Sonic hedgehog signalling. Nature 398, 622–627
    OpenUrlCrossRefPubMed
    1. Caric D.,
    2. Gooday D.,
    3. Hill R. E.,
    4. McConnell S. K.,
    5. Price D. J.
    (1997) Determination of the migratory capacity of embryonic cortical cells lacking the transcription factor Pax-6. Development 124, 5087–5096
    OpenUrlAbstract
    1. Casarosa S.,
    2. Fode C.,
    3. Guillemot F.
    (1999) Mash1 regulates neurogenesis in the ventral telencephalon. Development 126, 525–534
    OpenUrlAbstract
    1. Chapouton P.,
    2. Gartner A.,
    3. Gotz M.
    (1999) The role of Pax6 in restricting cell migration between developing cortex and basal ganglia. Development 126, 5569–5579
    OpenUrlAbstract
    1. Deacon T. W.,
    2. Pakzaban P.,
    3. Isacson O.
    (1994) The lateral ganglionic eminence is the origin of cells committed to striatal phenotypes: neural transplantation and developmental evidence. Brain Res 668, 211–219
    OpenUrlCrossRefPubMedWeb of Science
    1. Ericson J.,
    2. Muhr J.,
    3. Placzek M.,
    4. Lints T.,
    5. Jessell T. M.,
    6. Edlund T.
    (1995) Sonic hedgehog induces the differentiation of ventral forebrain neurons: a common signal for ventral patterning within the neural tube. Cell 81, 747–756
    OpenUrlCrossRefPubMedWeb of Science
    1. Ericson J.,
    2. Rashbass P.,
    3. Schedl A.,
    4. Brenner-Morton S.,
    5. Kawakami A.,
    6. van Heyningen V.,
    7. Jessell T. M.,
    8. Briscoe J.
    (1997) Pax6 controls progenitor cell identity and neuronal fate in response to graded Shh signaling. Cell 90, 169–180
    OpenUrlCrossRefPubMedWeb of Science
    1. Fode C.,
    2. Ma Q.,
    3. Casarosa S.,
    4. LeMeur M.,
    5. Dierich A.,
    6. Ang S.-L.,
    7. Anderson D. J.,
    8. Guillemot F.
    (2000) A role for neural determination genes in specifying the dorso-ventral identity of telencephalic neurons. Genes Dev 14, 67–80
    OpenUrlAbstract/FREE Full Text
    1. Frantz G. D.,
    2. Bohner A. P.,
    3. Akers R. M.,
    4. McConnell S. K.
    (1994) Regulation of the POU domain gene SCIP during cerebral cortical development. J. Neurosci 14, 472–485
    OpenUrlAbstract
    1. Furuta Y.,
    2. Piston D. W.,
    3. Hogan B. L.
    (1997) Bone morphogenetic proteins (BMPs) as regulators of dorsal forebrain development. Development 124, 2203–2212
    OpenUrlAbstract
    1. Gerfen C.R.
    (1990) The neostriatal mosaic: multiple levels of compartmental organization. Trends Neurosci 15, 133–139
    1. Guillemot F.,
    2. Joyner A. L.
    (1993) Dynamic expression of the murine Achaete-Scute homologue Mash-1 in the developing nervous system. Mech. Dev 42, 171–185
    OpenUrlCrossRefPubMedWeb of Science
    1. Götz M.,
    2. Stoykova A.,
    3. Gruss P.
    (1998) Pax6 controls radial glia differentiation in the cerebral cortex. Neuron 21, 1031–1044
    OpenUrlCrossRefPubMedWeb of Science
    1. Götz M.,
    2. Williams B. P.,
    3. Bolz J.,
    4. Price J.
    (1995) The specification of neuronal fate: a common precursor for neurotransmitter subtypes in the rat cerebral cortex in vitro. Eur. J. Neurosci 7, 889–898
    OpenUrlCrossRefPubMedWeb of Science
    1. Hallonet M.,
    2. Hollemann T.,
    3. Wehr R.,
    4. Jenkins N. A.,
    5. Copeland N. G.,
    6. Pieler T.,
    7. Gruss P.
    (1998) Vax1 is a novel homeobox-containing gene expressed in the developing anterior ventral forebrain. Development 125, 2599–2610
    OpenUrlAbstract
    1. Hill R. E.,
    2. Favor J.,
    3. Hogan B. L.,
    4. Ton C. C.,
    5. Saunders G. F.,
    6. Hanson I. M.,
    7. Prosser J.,
    8. Jordan T.,
    9. Hastie N. D.,
    10. van Heyningen V.
    (1991) Mouse small eye results from mutations in a paired-like homeobox-containing gene. Nature 354, 522–525
    OpenUrlCrossRefPubMed
    1. Horton S.,
    2. Meredith A.,
    3. Richardson J. A.,
    4. Johnson J. E.
    (1999) Correct coordination of neuronal differentiation events in ventral forebrain requires the bHLH factor MASH1. Mol. Cell. Neurosci 14, 355–369
    OpenUrlCrossRefPubMedWeb of Science
    1. Hsieh-Li H.,
    2. Witte D. P.,
    3. Szucsik J. C.,
    4. Weinstein M.,
    5. Li H.,
    6. Potter S. S.
    (1995) Gsh-2, a murine homeobox gene expressed in the developing brain. Mech. Dev 50, 177–186
    OpenUrlCrossRefPubMedWeb of Science
    1. Kohtz J. D.,
    2. Baker D. P.,
    3. Corte G.,
    4. Fishell G.
    (1998) Regionalization within the mammalian telencephalon is mediated by changes in responsiveness to Sonic Hedgehog. Development 125, 5079–5089
    OpenUrlAbstract
    1. Liem K. F., Jr.,
    2. Tremml G.,
    3. Jessell T. M.
    (1997) A role for the roof plate and its resident TGFbeta-related proteins in neuronal patterning in the dorsal spinal cord. Cell 91, 127–138
    OpenUrlCrossRefPubMedWeb of Science
    1. Liu J. K.,
    2. Ghattas I.,
    3. Liu S.,
    4. Chen S.,
    5. Rubenstein J. L.
    (1997) Dlx genes encode DNA-binding proteins that are expressed in an overlapping and sequential pattern during basal ganglia differentiation. Dev. Dyn 210, 498–512
    OpenUrlCrossRefPubMedWeb of Science
    1. Olsson M.,
    2. Campbell K.,
    3. Wictorin K.,
    4. Björklund A.
    (1995) Projection neurons in fetal striatal transplants are predominantly derived from the lateral ganglionic eminence. Neuroscience 69, 1169–1182
    OpenUrlCrossRefPubMedWeb of Science
    1. Olsson M.,
    2. Björklund A.,
    3. Campbell K.
    (1998) Early specification of striatal projection neurons and interneuronal subtypes in the lateral and medial ganglionic eminence. Neuroscience 84, 867–876
    OpenUrlCrossRefPubMedWeb of Science
    1. Parnavelas J. G.
    (2000) The origin and migration of cortical neurones: new vistas. Trends Neurosci 23, 126–131
    OpenUrlCrossRefPubMedWeb of Science
    1. Porteus M. H.,
    2. Bulfone A.,
    3. Liu J. K.,
    4. Puelles L.,
    5. Lo L. C.,
    6. Rubenstein J. L.
    (1994) DLX-2, MASH-1, and MAP-2 expression and bromodeoxyuridine incorporation define molecularly distinct cell populations in the embryonic mouse forebrain. J. Neurosci 14, 6370–6383
    OpenUrlAbstract
    1. Puelles L.,
    2. Kuwana E.,
    3. Puelles E.,
    4. Rubenstein J. L. R.
    (1999) Comparison of the mammalian and avian telencephalon from the perspective of gene expression data. Eur. J. Morphol 37, 139–150
    OpenUrlCrossRefPubMedWeb of Science
    1. Schluter C.,
    2. Duchrow M.,
    3. Wohlenberg C.,
    4. Becker M. H.,
    5. Key G.,
    6. Flad H. D.,
    7. Gerdes J.
    (1993) 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. J. Cell Biol 123, 513–522
    OpenUrlAbstract/FREE Full Text
    1. Schmahl W.,
    2. Knoedlseder M.,
    3. Favor J.,
    4. Davidson D.
    (1993) Defects of neuronal migration and the pathogenesis of cortical malformations are associated with Small eye (Sey) in the mouse, a point mutation at the Pax-6 -locus. Acta Neuropathol 86, 126–135
    OpenUrlCrossRefPubMed
    1. Shimamura K.,
    2. Hartigan D. J.,
    3. Martinez S.,
    4. Puelles L.,
    5. Rubenstein J. L.
    (1995) Longitudinal organization of the anterior neural plate and neural tube. Development 121, 3923–3933
    OpenUrlAbstract
    1. Simeone A.,
    2. Gulisano M.,
    3. Acampora D.,
    4. Stornaiuolo A.,
    5. Rambaldi M.,
    6. Boncinelli E.
    (1992) Two vertebrate homeobox genes related to the Drosophila empty spiracles gene are expressed in the embryonic cerebral cortex. EMBO J 11, 2541–2550
    OpenUrlPubMedWeb of Science
    1. Sommer L.,
    2. Ma Q.,
    3. Anderson D. J.
    (1996) Neurogenins, a novel family of atonal-related bHLH transcription factors, are putative mammalian neuronal determination genes that reveal progenitor cell heterogeneity in the developing CNS and PNS. Mol. Cell. Neurosci 8, 221–241
    OpenUrlCrossRefPubMedWeb of Science
    1. Stoykova A.,
    2. Fritsch R.,
    3. Walther C.,
    4. Gruss P.
    (1996) Forebrain patterning defects in Small eye mutant mice. Development 122, 3453–3465
    OpenUrlAbstract
    1. Stoykova A.,
    2. Götz M.,
    3. Gruss P.,
    4. Price J.
    (1997) Pax6 -dependent regulation of adhesive patterning, R-cadherin expression and boundary formation in the developing forebrain. Development 124, 3765–3777
    OpenUrlAbstract
    1. Sussel L.,
    2. Marin O.,
    3. Kimura S.,
    4. Rubenstein J. L.
    (1999). 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 126, 3359–3370
    OpenUrlAbstract
    1. Szucsik J. C.,
    2. Witte D. P.,
    3. Li H.,
    4. Pixley S. K.,
    5. Small K. M.,
    6. Potter S. S.
    (1997) Altered forebrain and hindbrain development in mice mutant for the Gsh-2 homeobox gene. Dev. Biol 191, 230–242
    OpenUrlCrossRefPubMedWeb of Science
    1. Tanabe Y.,
    2. Jessell T. M.
    (1996) Diversity and pattern in the developing spinal cord. Science 274, 1115–1123
    OpenUrlAbstract/FREE Full Text
    1. Toresson H.,
    2. Mata de Urquiza A.,
    3. Fagerström C.,
    4. Perlmann T.,
    5. Campbell K.
    (1999) Retinoids are produced by glia in the lateral ganglionic eminence and regulate striatal neuron differentiation. Development 126, 1317–1326
    OpenUrlAbstract
    1. Valerius M. T.,
    2. Li H.,
    3. Stock J. L.,
    4. Weinstein M.,
    5. Kaur S.,
    6. Singh G.,
    7. Potter S. S.
    (1995) Gsh-1: a novel murine homeobox gene expressed in the central nervous system. Dev. Dyn 203, 337–351
    OpenUrlPubMedWeb of Science
    1. van der Kooy D.,
    2. Fishell G.
    (1987) Neuronal birthdate underlies the development of striatal compartments. Brain Res 401, 155–161
    OpenUrlCrossRefPubMedWeb of Science
    1. Warren N.,
    2. Caric D.,
    3. Pratt T.,
    4. Clausen J. A.,
    5. Asavaritikrai P.,
    6. Mason J. O.,
    7. Hill R. E.,
    8. Price D. J.
    (1999) The transcription factor, Pax6, is required for cell proliferation and differentiation in the developing cerebral cortex. Cereb. Cortex 9, 627–635
    OpenUrlAbstract/FREE Full Text
    1. Weiss J. B.,
    2. Von Ohlen T.,
    3. Mellerick D. M.,
    4. Dressler G.,
    5. Doe C. Q.,
    6. Scott M. P.
    (1998) Dorsoventral patterning in the Drosophila central nervous system: the intermediate neuroblasts defective homeobox gene specifies intermediate column identity. Genes Dev 12, 3591–3602
    OpenUrlAbstract/FREE Full Text
    1. Yoshida M.,
    2. Suda Y.,
    3. Matsuo I.,
    4. Miyamoto N.,
    5. Takeda N.,
    6. Kuratani S.,
    7. Aizawa S.
    (1997) Emx1 and Emx2 functions in development of dorsal telencephalon. Development 124, 101–111
    OpenUrlAbstract
Back to top

 Download PDF

Email
JOURNAL ARTICLES
Genetic control of dorsal-ventral identity in the telencephalon: opposing roles for Pax6 and Gsh2
H. Toresson, S.S. Potter, K. Campbell
Development 2000 127: 4361-4371;
del.icio.us logo Digg logo Reddit logo Twitter logo CiteULike logo Facebook logo Google logo Mendeley logo
Citation Tools
Alerts

Article navigation

Other journals from The Company of Biologists

Advertisement

The Node is looking for a new Community Manager!

If you're interested in science communication, publishing and the developmental biology community, we're hiring for a new Community Manager for our community site, the Node.

The position is an exciting opportunity to develop an already successful and well-known site, engaging with the academic, publishing and online communities. Find out more and how to apply.

Upcoming special issue: call for papers

The Immune System in Development and Regeneration
Guest editors: Florent Ginhoux and Paul Martin
Submission deadline: 1 September 2021
Publication: Spring 2022

The special issue welcomes Review articles as well as Research articles, and will be widely promoted online and at key global conferences.

The people behind the papers - Clément Dubois, Shivam Gupta, Andrew Mugler and Marie-Anne Félix

A new paper investigates the robustness of neuroblast migration in the C. elegans larva in the face of both genetic and environmental variation. In an interview, the paper's four authors tell us more about the story.

Development presents...

Our successful webinar series continues into 2021, with early-career researchers presenting their papers and a chance to virtually network with the developmental biology community afterwards. Every talk is recorded and since launching in August last year, the series has clocked up almost 10k views on YouTube.

Here, Swann Floc'hlay discusses her work modelling dorsal-ventral axis specification in the sea urchin embryo.

Save your spot at our next session:

14 April
Time: 17:00 BST
Chaired by: François Guillemot

12 May
Time: TBC
Chaired by: Paola Arlotta

Join our mailing list to receive news and updates on the series.