Advertisement
JOURNAL ARTICLES
Gsh2 and Pax6 play complementary roles in dorsoventral patterning of the mammalian telencephalon
K. Yun, S. Potter, J.L. Rubenstein
Development 2001 128: 193-205;

Summary

The telencephalon has two major subdivisions, the pallium and subpallium. The pallium, which primarily consists of glutamatergic cortical structures, expresses dorsal molecular markers, whereas the subpallium, which primarily consists of the GABAergic basal ganglia, expresses ventral molecular markers. Here, we present evidence that the progenitor and postmitotic cells flanking the pallial/subpallial boundary (PSB) in the embryonic mouse can be subdivided into multiple regions that express unique combinations of transcription factors. The domains that immediately flank the PSB are the ventral pallium (VP) and the dorsal lateral ganglionic eminence (dLGE). The early expression of the Pax6 and Gsh2 homeobox transcription factors overlaps in the region of the dLGE. Analyses of mice that lack functional alleles of either Gsh2 or Pax6 demonstrate that these genes have complementary roles in patterning the primordia flanking the PSB. In the Gsh2 mutants, the dLGE is respecified into a VP-like structure, whereas in the Pax6 mutants the VP is respecified into a dLGE-like structure. The role of Pax6 in dorsalizing the telencephalon is similar to its role in the spinal cord, supporting the hypothesis that some dorsoventral patterning mechanisms are used at all axial levels of the central nervous system.

Reference

    1. Anderson S. A.,
    2. Eisenstat D. D.,
    3. Shi L.,
    4. Rubenstein J. L. R.
    (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. Qiu M.,
    3. Bulfone A.,
    4. Eisenstat D. D.,
    5. Meneses J.,
    6. Pedersen R.,
    7. Rubenstein J.L.R.
    (1997) Mutations of the homeobox genes 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. Anderson S.,
    2. Mione M.,
    3. Yun K.,
    4. Rubenstein J. L.R.
    (1999) Differential origins of neocortical projection and local circuit neurons: role of Dlx genes in neocortical interneuronogenesis. Cereb. Cortex 9, 646–654
    OpenUrlAbstract/FREE Full Text
    1. Bishop K. M.,
    2. Goudreau G.,
    3. O'Leary D.D.
    (2000) Regulation of area identity in the mammalian neocortex by Emx2 and Pax6. Science 288, 344–349
    OpenUrlAbstract/FREE Full Text
    1. Briscoe J.,
    2. Sussel L.,
    3. Serup P.,
    4. Hartigan-O'Connor D.,
    5. Jessell T. M.,
    6. Rubenstein J. L. R.,
    7. Ericson J.
    (1999). Homeobox gene Nkx2.2 and specification of neuronal identity by graded Sonic hedgehog signalling. Nature 398, 622–627
    OpenUrlCrossRefPubMed
    1. Briscoe J.,
    2. Pierani A.,
    3. Jessell T. M.,
    4. Ericson J.
    (2000) A homeodomain protein code specifies progenitor cell identity and neural fate in the ventral neural tube. Cell 101, 435–445
    OpenUrlCrossRefPubMedWeb of Science
    1. Bulfone A.,
    2. Kim H.-J.,
    3. Puelles L.,
    4. Porteus M. H.,
    5. Grippo J. F.,
    6. Rubenstein J. L. R.
    (1993) The mouse Dlx-2 (Tes-1) gene is expressed in spatially restricted domains of the forebrain, face and limbs in midgestation mouse embryos. Mech. Dev 40, 129–140
    OpenUrlCrossRefPubMedWeb of Science
    1. Bulfone A.,
    2. Wang F.,
    3. Hevner R.,
    4. Anderson S.,
    5. Cutforth T.,
    6. Chen S.,
    7. Meneses J.,
    8. Pedersen R.,
    9. Axel R.,
    10. Rubenstein J. L. R.
    (1998) An olfactory sensory map develops in the absence of normal projection neurons or GABAergic interneurons. Neuron 21, 1273–1282
    OpenUrlCrossRefPubMedWeb of Science
    1. Bulfone A.,
    2. Martinez S.,
    3. Marigo V.,
    4. Campanella M.,
    5. Basile A.,
    6. Quaderi N.,
    7. Gattuso C.,
    8. Rubenstein J. L.,
    9. Ballabio A.
    (1999) Expression pattern of the Tbr2 (Eomesodermin) gene during mouse and chick brain development. Mech. Dev 84, 133–138
    OpenUrlCrossRefPubMedWeb of Science
    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. Gärtner A.,
    3. Götz M.
    (1999) The role of Pax6 in restricting cell migration between developing cortex and basal ganglia. Development 126, 5569–5579
    OpenUrlAbstract
    1. Chiang C.,
    2. Litingtung Y.,
    3. Lee E.,
    4. Young K. E.,
    5. Corden J. L.,
    6. Westphal H.,
    7. Beachy P. A.
    (1996) Cyclopia and defective axial patterning in mice lacking Sonic hedgehog gene function. Nature 383, 407–413
    OpenUrlCrossRefPubMed
    1. Eisenstat D. D.,
    2. Liu J. K.,
    3. Mione M.,
    4. Zhong W.,
    5. Yu G.,
    6. Anderson S.,
    7. Ghatas I.,
    8. Puelles L.,
    9. Rubenstein J. L. R.
    (1999) DLX-1, DLX-2, and DLX-5 expression define distinct dtages of basal forebrain differentiation. J. Comp. Neurol 414, 217–237
    OpenUrlCrossRefPubMedWeb of Science
    1. Ericson J.,
    2. Briscoe J.,
    3. Rashbass P.,
    4. van Heyningen V.,
    5. Jessell T. M.
    (1997) Graded sonic hedgehog signaling and the specification of cell fate in the ventral neural tube. Cold Spring Harb. Symp. Quant. Biol 62, 451–466
    OpenUrlAbstract/FREE Full Text
    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. Fishell G.,
    2. Mason C.A.,
    3. Hatten M. E.
    (1993) Dispersion of neural progenitors within the germinal zones of the forebrain. Nature 362, 636–638
    OpenUrlCrossRefPubMed
    1. Fode C.,
    2. Ma Q.,
    3. Casarosa S.,
    4. Ang S. L.,
    5. Anderson D. J.,
    6. Guillemot F.
    (2000) A role for neural determination genes in specifying the dorsoventral identity of telencephalic neurons. Genes Dev 14, 67–80
    OpenUrlAbstract/FREE Full Text
    1. Galceran J.,
    2. Miyashita-Lin E. M.,
    3. Devaney E.,
    4. Rubenstein J. L. R.,
    5. Grosschedl R.
    (2000) Hippocampus development and generation of dentate gyrus granule cells is regulated by LEF1. Development 127, 469–482
    OpenUrlAbstract
    1. Goldman S. A.,
    2. Luskin M. B.
    (1998) Strategies utilized by migrating neurons of the postnatal vertebrate forebrain. Trends Neurosci 21, 107–114
    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. Grindley J. C.,
    2. Hargett L. K.,
    3. Hill R. E.,
    4. Ross A.,
    5. Hogan B. L.
    (1997) Disruption of PAX6 function in mice homozygous for the Pax6Sey-1Neu mutation produces abnormalities in the early development and regionalization of the diencephalon. Mech. Dev 64, 111–126
    OpenUrlCrossRefPubMedWeb of Science
    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. Richarson 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. M.,
    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. Lavdas A. A.,
    2. Grigoriou M.,
    3. Pachnis V.,
    4. Parnavelas J. G.
    (1999) The medial ganglionic eminence gives rise to a population of early neurons in the developing cerebral cortex. J. Neurosci 99, 7881–7888
    1. Lee K. J.,
    2. Jessell T. M.
    (1999) The specification of dorsal cell fates in the vertebrate central nervous system. Annu. Rev. Neurosci 22, 261–294
    OpenUrlCrossRefPubMedWeb of Science
    1. Lee S. M.,
    2. Tole S.,
    3. Grove E.,
    4. McMahon A. P.
    (2000) A local Wnt-3a signal is required for development of the mammalian hippocampus. Development 127, 457–467
    OpenUrlAbstract
    1. Li H.,
    2. Zeitler P. S.,
    3. Valerius M. T.,
    4. Small K.,
    5. Potter S. S.
    (1996) Gsh-1, an orphan Hox gene, is required for normal pituitary development. EMBO J 15, 714–724
    OpenUrlPubMedWeb of Science
    1. Lu S.,
    2. Bogarad L. D.,
    3. Murtha M. T.,
    4. Ruddle F. H.
    (1992) Expression pattern of a murine homeobox gene, Dbx, displays extreme spatial restriction in embryonic forebrain and spinal cord. Proc. Natl. Acad. Sci. USA 89, 8053–8057
    OpenUrlAbstract/FREE Full Text
    1. Marín O.,
    2. Anderson S. A.,
    3. Rubenstein J. L. R.
    (2000) Origin and molecular specification of striatal interneurons,. J. Neurosci 20, 6063–6076
    OpenUrlAbstract/FREE Full Text
    1. Mastick G. S.,
    2. Davis N. M.,
    3. Andrew G. L.,
    4. Easter S. S., Jr
    (1997) Pax-6 functions in boundary formation and axon guidance in the embryonic mouse forebrain. Development 124, 1985–1997
    OpenUrlAbstract
    1. Oliver G.,
    2. Mailhos A.,
    3. Wehr R.,
    4. Copeland N. G.,
    5. Jenkins N. A.,
    6. Gruss P.
    (1995) Six3, a murine homologue of the sine oculis gene, demarcates the most anterior border of the developing neural plate and is expressed during eye development. Development 121, 4045–4055
    OpenUrlAbstract
    1. Osumi N.,
    2. Hirota A.,
    3. Ohuchi H.,
    4. Nakafuku M.,
    5. Iimura T.,
    6. Kuratani S.,
    7. Fujiwara M.,
    8. Noji S.,
    9. Eto K.
    (1997) Pax-6 is involved in the specification of hindbrain motor neuron subtype. Development 124, 2961–2967
    OpenUrlAbstract
    1. Pierani A.,
    2. Brenner-Morton S.,
    3. Chiang C.,
    4. Jessell T. M.
    (1999) A sonic hedgehog-independent, retinoid-activated pathway of neurogenesis in the ventral spinal cord. Cell 97, 903–915
    OpenUrlCrossRefPubMedWeb of Science
    1. Porter F. D.,
    2. Drago J.,
    3. Xu Y.,
    4. Cheema S. S.,
    5. Wassif C.,
    6. Huang S. P.,
    7. Lee E.,
    8. Grinberg A.,
    9. Massalas J. S.,
    10. Bodine D.,
    11. Alt F.,
    12. Westphal H.
    (1997) Lhx2, a LIM homeobox gene, is required for eye, forebrain, and definitive erythrocyte development. Development 124, 2935–2944
    OpenUrlAbstract
    1. Porteus M. H.,
    2. Bulfone A.,
    3. Liu J. K.,
    4. Puelles L.,
    5. Lo L. C.,
    6. Rubenstein J. L. R.
    (1994) DLX-2, MASH-1, 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. Bulfone A.,
    5. Shimamura K.,
    6. Keleher J.,
    7. Smiga S.,
    8. Rubenstein J. L. R.
    (2000). Pallial and subpallial derivatives in the embryonic chick and mouse telencephalon, traced by the expression of the genes Dlx-2, Emx-1, Nkx-2.1, Pax-6 and Tbr-1. J. Comp. Neurol 424, 409–438
    OpenUrlCrossRefPubMedWeb of Science
    1. Qiu M.,
    2. Bulfone A.,
    3. Martinez S.,
    4. Meneses J. J.,
    5. Shimamura K.,
    6. Pedersen R. A.,
    7. Rubenstein J. L. R.
    (1995) Role of Dlx-2 in head development and evolution: null mutation of Dlx-2 results in abnormal morphogenesis of proximal first and second branchial arch derivatives and abnormal differentiation in the forebrain. Genes Dev 9, 2523–2538
    OpenUrlAbstract/FREE Full Text
    1. Qiu M.,
    2. Shimamura K.,
    3. Sussel L.,
    4. Chen S.,
    5. Rubenstein J. L. R.
    (1998). Control of anteroposterior and dorsoventral domains of Nkx-6.1 gene expression relative to other Nkx genes during vertebrate CNS development. Mech. Dev 72, 77–88
    OpenUrlCrossRefPubMedWeb of Science
    1. Sander M.,
    2. Paydar S.,
    3. Ericson J.,
    4. Briscoe J.,
    5. Berber E.,
    6. German M.,
    7. Jessell. T.,
    8. Rubenstein J. L. R.
    (2000). Ventral neural patterning by Nkx homeobox genes: Nkx6.1 control somatic motor neuron and ventral interneuron fates. Genes Dev 14, 2134–2139
    OpenUrlAbstract/FREE Full Text
    1. Sheth A. N.,
    2. Bhide P. G.
    (1997) Concurrent cellular output from two proliferative populations in the early embryonic mouse corpus striatum. J. Comp. Neurol 383, 220–230
    OpenUrlCrossRefPubMedWeb of Science
    1. Shoji H.,
    2. Ito T.,
    3. Wakamatsu Y.,
    4. Hayasaka N.,
    5. Ohsaki K.,
    6. Oyanagi M.,
    7. Kominami R.,
    8. Kondoh H.,
    9. Takahashi N.
    (1996) Regionalized expression of the Dbx family homeobox genes in the embryonic CNS of the mouse. Mech. Dev 56, 25–39
    OpenUrlCrossRefPubMedWeb of Science
    1. Smith-Fernández A.,
    2. Pieau C.,
    3. Reperant J.,
    4. Boncinelli E.,
    5. Wassef M.
    (1998) Expression of the Emx-1 and Dlx-1 homeobox genes define three molecularly distinct domains in the telencephalon of mouse, chick, turtleand frog embryos: implications for the evolution of telencephalic subdivisions in amniotes. Development 125, 2099–2111
    OpenUrlAbstract
    1. Solloway M. J.,
    2. Robertson E. J.
    (1999) Early embryonic lethality in Bmp5;Bmp7 double mutant mice suggests functional redundancy within the 60A subgroup. Development 126, 1753–1768
    OpenUrlAbstract
    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 developing forebrain. Development 124, 3765–3777
    OpenUrlAbstract
    1. Sussel L.,
    2. Marín O.,
    3. Kimura S.,
    4. Rubenstein J. L. R.
    (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. 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. Valverde F.,
    2. García C.,
    3. Lopez-Mascaraque L.,
    4. De Carlos J. A.
    (2000) Development of the mammillothalamic tract in normal and Pax-6 mutant mice. J. Comp. Neurol 419, 485–504
    OpenUrlCrossRefPubMedWeb 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. Warren N.,
    2. Price D. J.
    (1997) Roles of Pax-6 in murine diencephalic development. Development 124, 1573–1582
    OpenUrlAbstract
    1. Wawersik S.,
    2. Purcell P.,
    3. Rauchman M.,
    4. Dudley A.T.,
    5. Robertson E.J.,
    6. Mass R.
    (1999) BMP7 acts in murine lens placode development. Dev. Biol 207, 176–188
    OpenUrlCrossRefPubMedWeb of Science
Back to top

 Download PDF

Email
JOURNAL ARTICLES
Gsh2 and Pax6 play complementary roles in dorsoventral patterning of the mammalian telencephalon
K. Yun, S. Potter, J.L. Rubenstein
Development 2001 128: 193-205;
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

A new society for regenerative biologists

Kenneth Poss and Elly Tanaka announce the launch of the International Society for Regenerative Biology (ISRB), which will promote research and education in the field of regenerative biology.

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.

An interview with Cagney Coomer

Over a virtual chat, we spoke to Cagney Coomer about her experiences in the lab, the classroom and the community centre, and why she thinks outreach and role models are vital to science.

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. Here, Michèle Romanos talks about her new preprint, which mixes experimentation in quail embryos and computational modelling to understand how heterogeneity in a tissue influences cell rate.

Save your spot at our next session:

10 March
Time: 9:00 (GMT)
Chaired by: Thomas Lecuit

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