Advertisement
JOURNAL ARTICLES
Ace/Fgf8 is required for forebrain commissure formation and patterning of the telencephalon
S. Shanmugalingam, C. Houart, A. Picker, F. Reifers, R. Macdonald, A. Barth, K. Griffin, M. Brand, S.W. Wilson
Development 2000 127: 2549-2561;

Summary

Fibroblast growth factors (Fgfs) form a large family of secreted signalling proteins that have a wide variety of roles during embryonic development. Within the central nervous system (CNS) Fgf8 is implicated in patterning neural tissue adjacent to the midbrain-hindbrain boundary. However, the roles of Fgfs in CNS tissue rostral to the midbrain are less clear. Here we examine the patterning of the forebrain in zebrafish embryos that lack functional Fgf8/Ace. We find that Ace is required for the development of midline structures in the forebrain. In the absence of Ace activity, midline cells fail to adopt their normal morphology and exhibit altered patterns of gene expression. This disruption to midline tissue leads to severe commissural axon pathway defects, including misprojections from the eye to ectopic ipsilateral and contralateral targets. Ace is also required for the differentiation of the basal telencephalon and several populations of putative telencephalic neurons but not for overall regional patterning of forebrain derivatives. Finally, we show that ace expression co-localises with anterior neural plate cells that have previously been shown to have forebrain patterning activity. Removal of these cells leads to a failure in induction of ace expression indicating that loss of Ace activity may contribute to the phenotypes observed when anterior neural plate cells are ablated. However, as ace mutant neural plate cells still retain at least some inductive activity, then other signals must also be produced by the anterior margin of the neural plate.

REFERENCES

    1. Amaya E.,
    2. Musci T. J.,
    3. Kirschner M. W.
    (1991) Expression of a dominant negative mutant of the FGF receptor disrupts mesoderm formation in Xenopus embryos. Cell 66, 257–270
    OpenUrlCrossRefPubMedWeb of Science
    1. Barth K. A.,
    2. Kishimoto Y.,
    3. Rohr K. B.,
    4. Seydler C.,
    5. Schulte-Merker S.,
    6. Wilson S. W.
    (1999) Bmp/Swirl activity establishes a gradient of positional information throughout the entire neural plate. Development 126, 4977–4987
    OpenUrlAbstract
    1. Beddington R. S. P.,
    2. Robertson E. J.
    (1999) Axis development and early asymmetry in mammals. Cell 96, 195–209
    OpenUrlCrossRefPubMedWeb of Science
    1. Blader P.,
    2. Strähle U.
    (1998) Casting an eye over cyclopia. Nature 395, 112–113
    OpenUrlCrossRefPubMed
    1. Brand M.,
    2. Heisenberg C. P.,
    3. Jiang Y.,
    4. Beuchle D.,
    5. Lun K.,
    6. Furutani-Seki M.,
    7. Granato M.,
    8. Hafter P.,
    9. Hamerschmidt M.,
    10. Kane D. A.,
    11. Kelsh R. N.,
    12. Mullins M.,
    13. Odenthal J.,
    14. van Eeden F. J. M.,
    15. Nusslein-Volhard C.
    (1996) Mutations in zebrafish genes affecting the formation of the boundary between mid-hindbrain. Development 123, 179–190
    OpenUrlAbstract/FREE Full Text
    1. Bulfone A.,
    2. Smiga S. M.,
    3. Shimamura K.,
    4. Peterson A.,
    5. Puelles L.,
    6. Rubenstein J. L. R.
    (1995) T-brain-1: a homolog of Brachyury whose expression defines molecularly distinct domains within the cerebral cortex. Neuron 15, 63–78
    OpenUrlCrossRefPubMedWeb of Science
    1. Burrill J. D.,
    2. Easter S. S. J.
    (1994) Development of the retinofugal projections in the embryonic and larval zebrafish. J. Comp. Neurol 346, 583–600
    OpenUrlCrossRefPubMedWeb of Science
    1. Burrill J. D.,
    2. Easter S. S. J.
    (1995) The first retinal axons and their microenvironment in Zebrafish: cryptic pioneers and pretract. J. Neurosci 15, 2935–2947
    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
    OpenUrlCrossRefPubMedWeb of Science
    1. Cook G.,
    2. Tannahill D.,
    3. Keynes R.
    (1998) Axon guidance to and from choice points. Curr. Opin. Neurobiol 8, 64–72
    OpenUrlCrossRefPubMedWeb of Science
    1. de la Torre J. R.,
    2. Hopker V. H.,
    3. Ming G.,
    4. Poo M.,
    5. Tessier-Lavigne M.,
    6. Hemmati-Brinvanlou A.,
    7. Holt C. E.
    (1997) Turning of retinal growth cones in a netrin-1 gradient mediated by the netrin receptor DCC. Neuron 19, 1211–1224
    OpenUrlCrossRefPubMedWeb of Science
    1. Deiner M. S.,
    2. Kennedy T. E.,
    3. Fazeli A.,
    4. Serafini T.,
    5. Tessier-Lavigne M.,
    6. Sretavan D. W.
    (1997) Netrin-1 and DCC mediate axon guidance locally at the optic disc: loss of function leads to optic nerve hypoplasia. Neuron 19, 575–589
    OpenUrlCrossRefPubMedWeb of Science
    1. Deiner M. S.,
    2. Sretavan D. W.
    (1999) Altered midline axon pathways and ectopic neurons in the developing hypothalamus of netrin-1-and DCC-deficient mice. J. Neurosci 19, 9900–9912
    OpenUrlAbstract/FREE Full Text
    1. Eagleson G.,
    2. Ferreiro B.,
    3. Harris W. A.
    (1995) Fate of the anterior neural ridge and the morphogenesis of the Xenopus forebrain. J. Neurobiol 28, 146–158
    OpenUrlCrossRefPubMed
    1. Ekker S. C.,
    2. Ungar A. R.,
    3. Greenstein P.,
    4. von Kessler D. P.,
    5. Porter J. A.,
    6. Moon. R. T.,
    7. Beachy P. A.
    (1995) Patterning activities of vertebrate hedgehog proteins in the developing eye and brain. Curr. Biol 5, 944–955
    OpenUrlCrossRefPubMedWeb of Science
    1. Ericson J.,
    2. Norlin S.,
    3. Jessell T. M.,
    4. Edlund T.
    (1998) Integrated FGF and BMP signalling controls the progression of progenitor cell differentiation and emergence of pattern in the embryonic anterior pituitary. Development 125, 1005–1015
    OpenUrlAbstract
    1. Furuta Y.,
    2. Piston D. W.,
    3. Hogan B. M.
    (1997) Bone morphogenetic proteins (BMPs) as regulators of dorsal forebrain development. Development 124, 2203–2212
    OpenUrlAbstract
    1. Griffin K.,
    2. Patient R.,
    3. Holder N.
    (1995) Analysis of FGF function in normal and no tail zebrafish embryos reveals separate mechanisms for formation of the trunk and tail. Development 121, 2983–2994
    OpenUrlAbstract
    1. Golden J. A.,
    2. Brachilovic A.,
    3. McFadden K. A.,
    4. Beesley J. S.,
    5. Rubenstein J. L. R.,
    6. Grinspan J. B.
    (1999) Ectopic bone morphogenetic proteins 5 and 4 in the chick forebrain lead to cyclopia and holoprosencephaly. Proc. Natl. Acad. Sci. USA 96, 2439–2444
    OpenUrlAbstract/FREE Full Text
    1. Gong Q.,
    2. Shipley M.
    (1995) Evidence that pioneer olfactory axons regulate telencephalic cell cycle kinetics to induce the formation of the olfactory bulb. Neuron 14, 91–101
    OpenUrlCrossRefPubMedWeb of Science
    1. Graziadei P. P. C.,
    2. Monti-Graziadei A. G.
    (1992) The influence of the olfactory placode on the development of the telencephalon in Xenopus laevis. Neuroscience 46, 617–629
    OpenUrlCrossRefPubMedWeb of Science
    1. Gulisano M.,
    2. Broccoli V.,
    3. Pardini C.,
    4. Boncinelli E.
    (1996) Emx1 and Emx2 show different patterns of expression during proliferation and differentiation of the developing cerebral cortex in the mouse. Eur. J. Neurosci 8, 1037–1050
    OpenUrlCrossRefPubMedWeb of Science
    1. Halloran M. C.,
    2. Severance S. M.,
    3. Yee C. S.,
    4. Gemza D. L.,
    5. Raper J. A.,
    6. Kuwada J. Y.
    (1999) Analysis of a zebrafish semaphorin reveals potential functions in vivo. Dev. Dyn 214, 13–25
    OpenUrlCrossRefPubMedWeb of Science
    1. Heisenberg C. P.,
    2. Brennan C.,
    3. Wilson S. W.
    (1999) Zebrafish aussicht mutant embryos exhibit widespread overexpression of ace (fgf8) and coincedent defects in CNS development. Development 126, 2129–2140
    OpenUrlAbstract
    1. Houart C.,
    2. Westerfield M.,
    3. Wilson S. W.
    (1998) A small population of anterior cells pattern the forebrain during zebrafish gastrulation. Nature 391, 788–792
    OpenUrlCrossRefPubMed
    1. Karlstrom R. O.,
    2. Talbot W. S.,
    3. Schier A. F.
    (1999) Comparative synteny cloning of zebrafish you-too: mutations in the Hedgehog target gli2 affect ventral forebrain patterning. Genes Dev 13, 388–393
    OpenUrlAbstract/FREE Full Text
    1. Kazanskaya O. V.,
    2. Severtzova E. A.,
    3. Barth K. A.,
    4. Ermakova G. V.,
    5. Lukyanov S. A.,
    6. Benyumov A.,
    7. Pannese M.,
    8. Boncinelli E.,
    9. Wilson S. W.,
    10. Zaraisky A. G.
    (1997) ANF: a novel class of homeobox genes expressed at the anterior end of the embryonic axis of vertebrates. Gene 200, 225–234
    OpenUrl
    1. Kimmel C. B.,
    2. Balard W. W.,
    3. Kimmel S. R.,
    4. Ullmann B.,
    5. Schilling T. F.
    (1995) Stages of embryonic development of the zebrafish. Dev.Dyn 203, 253–310
    OpenUrlCrossRefPubMedWeb of Science
    1. Kobayashi M.,
    2. Toyama R.,
    3. Takeda H.,
    4. Dawid I. B.,
    5. Kawakami K.
    (1998) Overexpression of the forebrain specific homeobox gene six3 induces rostral forebrain enlargement in zebrafish. Development 125, 2973–2982
    OpenUrlAbstract
    1. Lumsden A.
    (1995) A ‘LIM code’ for motor neurons?. Curr. Biol 5, 491–495
    OpenUrlCrossRefPubMedWeb of Science
    1. Lun K.,
    2. Brand M.
    (1998). A series of no isthmus (noi) alleles of the zebrafish pax2.1 gene reveals multiple signaling events in development of the midbrain-hindbrain boundary. Development 125, 3049–3062
    OpenUrlAbstract
    1. Macdonald R.,
    2. Barth K. A.,
    3. Xu Q.,
    4. Holder N.,
    5. Mikkola I.,
    6. Wilson S. W.
    (1995) Midline signalling is required for Pax gene regulation and patterning of the eyes. Development 121, 3267–3278
    OpenUrlAbstract
    1. Macdonald R.,
    2. Scholes J.,
    3. Strähle U.,
    4. Brennan C.,
    5. Holder N.,
    6. Brand M.,
    7. Wilson S. W.
    (1997) The Pax protein Noi is required for commissural axon pathway formation in the rostral forebrain. Development 124, 2397–2408
    OpenUrlAbstract
    1. Marcus R. C.,
    2. Easter S. S., Jr
    (1995) Expression of glial fibrillary acidic protein and its relation to tract formation in embryonic zebrafish (Danio rerio). J. Comp. Neurol 359, 365–381
    OpenUrlCrossRefPubMedWeb of Science
    1. McCabe K. L.,
    2. Gunther E. C.,
    3. Reh T. A.
    (1999) The development of the pattern of retinal ganglion cells in the chick retina: mechanisms that control differentiation. Development 126, 5713–5724
    OpenUrlAbstract
    1. McFarlane S.,
    2. McNeil L.,
    3. Holt C. E.
    (1995) FGF signalling and target recognition in the developing Xenopus visual system. Neuron 15, 1017–1028
    OpenUrlCrossRefPubMedWeb of Science
    1. McFarlane S.,
    2. Cornel E.,
    3. Amaya E.,
    4. Holt C. E.
    (1996) FGF receptor activity in retinal ganglion cell axons cause errors in target recognition. Neuron 17, 245–254
    OpenUrlCrossRefPubMedWeb of Science
    1. Meyers E. N.,
    2. Lewandoski M.,
    3. Martin G. R.
    (1998) A Fgf8 mutant allelic series generated by Cre-and Flp-mediated recombination. Nature Genet 18, 136–141
    OpenUrlCrossRefPubMedWeb of Science
    1. Mohammadi M.,
    2. McMahon G.,
    3. Sun L.,
    4. Tang C.,
    5. Hirth P.,
    6. Yeh B. K.,
    7. Hubbard S. R.,
    8. Sclessinger J.
    (1997) Structures of the tyrosine kinase domain of fibroblast growth factor in complex with inhibitors. Science 276, 955–960
    OpenUrlAbstract/FREE Full Text
    1. Morita T.,
    2. Nitta H.,
    3. Kiyama Y.,
    4. Mori H.,
    5. Mishina M.
    (1995) Different expression of two zebrafish emx homeoprotein mRNAs in the developing brain. Neurosci. Lett 198, 131–134
    OpenUrlCrossRefPubMedWeb of Science
    1. Picker A.,
    2. Brennan C.,
    3. Reifers F.,
    4. Clarke J. D. W.,
    5. Holder N.,
    6. Brand M.
    (1999) Requirement for the zebrafish mid-hindbrain boundary in midbrain polarisation, mapping and confinement of the retinotectal projection. Development 126, 2967–2978
    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) DLX2, 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. Reifers F.,
    2. Bohli H.,
    3. Walsh E. C.,
    4. Crossley P. H.,
    5. Stainier D. Y. R.,
    6. Brand M.
    (1998) Fgf8 is mutated in zebrafish acerebellar (ace) mutantsand is required for maintenance of mid-hindbrain boundary development and somitogenesis. Development 125, 2381–2395
    OpenUrlAbstract
    1. Reifers F.,
    2. Walsh E. C.,
    3. Leger S.,
    4. Stainier D. Y. R.,
    5. Brand M.
    (2000) Induction and differentiation of the zebrafish heart requires fibroblast growth factor 8 (fgf8/acerebellar). Development 127, 225–235
    OpenUrlAbstract
    1. Schauerte H. E.,
    2. van Eeden F. J. M.,
    3. Frickle C.,
    4. Odenthal J.,
    5. Strahle U.,
    6. Haffter P.
    (1998) Sonic hedgehog is not required for the induction of medial floor plate cells in the zebrafish. Development 125, 2983–2993
    OpenUrlAbstract
    1. Shimamura K.,
    2. Rubenstein J. L. R.
    (1997) Inductive interactions direct early regionalisation of the mouse forebrain. Development 124, 2709–2718
    OpenUrlAbstract
    1. Strahle U.,
    2. Fischer N.,
    3. Blader P.
    (1997) Expression and regulation of a netrin homologue in the zebrafish. Mech. Dev 62, 147–160
    OpenUrlCrossRefPubMedWeb of Science
    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. Toyama R.,
    2. Dawid I. B.
    (1997) lim6, a novel LIM homeobox gene in the zebrafish: comparison of its expression with lim1. Dev. Dyn 209, 406–417
    OpenUrlCrossRefPubMed
    1. Tucker A. S.,
    2. Yamada G.,
    3. Grigoriou M.,
    4. Pachnis V.,
    5. Sharpe P. T.
    (1999) Fgf-8 determines rostral-caudal polarity in the first branchial arch. Development 126, 51–61
    OpenUrlAbstract
    1. Varga Z. M.,
    2. Wegner J.,
    3. Westerfield M.
    (1999) Anterior movement of ventral diencephalic precursors separates the primordial eye field in the neural plate and requires cyclops. Development 126, 5533–5546
    OpenUrlAbstract
    1. Wang F.,
    2. Nemes A.,
    3. Mendelsohn M.,
    4. Axel R.
    (1998) Odorant receptors govern the formation of a precise topographic map. Cell 93, 47–60
    OpenUrlCrossRefPubMedWeb of Science
    1. Whitlock K. E.,
    2. Westerfield M.
    (1998) Transient population of neurons pioneers the olfactory pathway in the zebrafish. J. Neurosci 18, 8919–8927
    OpenUrlAbstract/FREE Full Text
    1. Wilson S. W.,
    2. Ross L. S.,
    3. Parret T.,
    4. Easter S. S., Jr
    (1990) The development of a simple scaffold axon tracts in the brain of the embryonic zebrafish. Development 108, 121–145
    OpenUrlAbstract
    1. Wilson S. W.,
    2. Easter S. S., Jr
    (1991) Stereotyped pathfinding by growth cones of early epiphysial neurons in the embryonic epiphysis. Development 112, 723–746
    OpenUrlAbstract
    1. Ye W.,
    2. Shimamura K.,
    3. Rubenstein J. L. R.,
    4. Hynes M. A.,
    5. Rosenthal A.
    (1998) FGF and Shh signals control dopaminergic cell fate in the anterior neural plate. Cell 93, 7755–766
    OpenUrl
Back to top

 Download PDF

Email
JOURNAL ARTICLES
Ace/Fgf8 is required for forebrain commissure formation and patterning of the telencephalon
S. Shanmugalingam, C. Houart, A. Picker, F. Reifers, R. Macdonald, A. Barth, K. Griffin, M. Brand, S.W. Wilson
Development 2000 127: 2549-2561;
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

An interview with Swathi Arur

Swathi Arur joined the team at Development as an Academic Editor in 2020. Her lab uses multidisciplinary approaches to understand female germline development and fertility. We met with her over Zoom to hear more about her life, her career and her love for C. elegans.

Jim Wells and Hanna Mikkola join our team of Editors

We are pleased to welcome James (Jim) Wells and Hanna Mikkola to our team of Editors. Jim joins us a new Academic Editor, taking over from Gordan Keller, and Hanna joins our team of Associate Editors. Find out more about their research interests and areas of expertise.

New funding scheme supports sustainable events

As part of our Sustainable Conferencing Initiative, we are pleased to announce funding for organisers that seek to reduce the environmental footprint of their event. The next deadline to apply for a Scientific Meeting grant is 26 March 2021.

Read & Publish participation continues to grow

“I’d heard of Read & Publish deals and knew that many universities, including mine, had signed up to them but I had not previously understood the benefits that these deals bring to authors who work at those universities.”

Professor Sally Lowell (University of Edinburgh) shares her experience of publishing Open Access as part of our growing Read & Publish initiative. We now have over 150 institutions in 15 countries and four library consortia taking part – find out more and view our full list of participating institutions.

Upcoming special issues

Imaging Development, Stem Cells and Regeneration
Submission deadline: 30 March 2021
Publication: mid-2021

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

Both special issues welcome Review articles as well as Research articles, and will be widely promoted online and at key global conferences.

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, Brandon Carpenter talks about how inherited histone methylation defines the germline versus soma decision in C. elegans. 

Sign up to join our next session:

10 March
Time: TBC
Chaired by: Thomas Lecuit