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Clare Baker PhD

Reader in Comparative Developmental Neurobiology
Tel: +44 (0)1223 333789, Fax: +44 (0)1223 333786, E-mail: cvhb1@cam.ac.uk

Neurogenic placodes and the neural crest: development and evolution of the vertebrate head

Neurogenic placodes and the neural crest are two distinct embryonic cell populations that are crucial for the development of the vertebrate head. Together, they give rise to the whole peripheral nervous system, i.e., all the sensory receptor cells, neurons (nerve cells) and glial cells (nerve-support cells) located outside the brain and spinal cord. Neural crest cells also build much of the craniofacial skeleton.

Neurogenic placodes (paired patches of thickened surface ectoderm in the embryonic head) give rise to the paired peripheral sense organs: the olfactory placodes form the olfactory receptor neurons in the nose that detect smells; the otic placodes form the inner ears, in which fluid movement (due to sound waves or head motion) stimulates mechanosensory hair cells, giving us our senses of hearing and balance; and a series of lateral line placodes forms the lateral line system of fish and aquatic-stage amphibians, in which mechanosensory hair cells (very like those in the inner ear), distributed in lines over the head and flank, detect local water movement for e.g. prey/predator detection and schooling behaviour. Neurogenic placodes also form the hormone-producing cells of the anterior pituitary gland, the eye lenses, and most of the peripheral sensory neurons of the head, collected in discrete cranial sensory ganglia.

Neural crest cells migrate out of the developing brain and spinal cord: they give rise to all the other neurons and all glial cells of the peripheral nervous system, plus a wide variety of other cell types including pigment cells, most of the cartilages and bones of the face and skull, and the dentine-producing cells of teeth.

We are investigating a broad range of questions relating to the development of neurogenic placodes and the neural crest. Current projects include:
the development of olfactory ensheathing glia
the development and evolution of electroreceptors
the role of Pax genes in neurogenic placode development
the development and evolution of the neural crest-derived pharyngeal skeleton

Development of olfactory ensheathing glia: Using grafting techniques in chicken embryos and genetic lineage-tracing in mice, we have recently discovered that olfactory ensheathing cells (OECs, which ensheath and protect olfactory nerve fibres) are derived from the neural crest, like all other peripheral glial cells, and not from the olfactory placodes as previously thought (Barraud et al., 2010, Proc. Natl. Acad. Sci. USA). Excitingly, OECs can promote nerve repair when transplanted into the damaged spinal cord, but it has proved difficult to isolate them in large enough numbers from the nose for effective therapy. Neural crest stem cells persist in adult skin and hair follicles, and it is possible to isolate these stem cells and grow them in the lab. The next step is to work out how to turn these stem cells into OECs: to do this, we need to investigate how this process happens normally in the developing embryo. We are currently investigating this question, as well as the role of OECs during the embryonic development of the olfactory system.

Development and evolution of electroreceptors: Land vertebrates, as well as frogs and most modern bony fish, have lost one of the most ancient vertebrate senses, the ability to detect weak electric fields in water, used for finding prey and for orientation. Electroreceptors are modified hair cells, distributed in fields of "ampullary organs" on either side of the lateral lines of mechanosensory hair cells. They are found in all major aquatic vertebrate groups, including jawless fish (lampreys), cartilaginous fish (sharks, rays), primitive bony fish (e.g. sturgeon, paddlefish), and even some amphibians (salamanders). Although the ancestors of teleosts (modern bony fish) lost electroreceptors, so that most of these fish cannot detect electric fields, electroreceptors seem to have been independently "re-invented" at least twice in two different groupsof teleosts, including catfish and "electric fish". (For more information on vertebrate electroreception, see Map Of Life). Very little is known about electroreceptor development. We are investigating the embryological origins of electroreceptors, and the genes underlying their formation, in a wide range of vertebrate groups including shark, paddlefish, salamander and catfish.

Role of Pax genes in neurogenic placode development: Neurogenic placodes are relatively simple, accessible model systems for studying how cells adopt a specific sensory cell fate, since neurons arising from different placodes innervate different targets and transmit different kinds of sensory information. Different members of the Pax family of paired-box transcription factors are expressed in different placodes: Pax6 is required for the development of the olfactory and lens placodes; Pax3 is expressed in the ophthalmic trigeminal placode, while Pax2 is expressed in the epibranchial and otic placodes. We are interested in understanding the role of Pax genes in neurogenic placode development. The chicken embryo is our model system of choice for this work because it is readily accessible for microsurgery and cell-marking techniques, and gene expression can be manipulated both spatially and temporally by targeted in ovo electroporation.

Development and evolution of the neural crest-derived pharyngeal skeleton: Dr Andrew Gillis, a Royal Society Newton International Fellow in the lab from 2009-2011, worked on a variety of questions relating to the formation of the neural crest-derived skeleton of the jaws and more posterior pharyngeal arches. For further details, please see his webpage.

Research Team
Dr Perrine Barraud
Dr Melinda Modrell
Sophie Miller (PhD Student)
Connie Rich (PhD Student)

Former Members of Research Team
Dr Paul O'Neill, currently a RIKEN postdoctoral fellow with Dr Raj Ladher at the RIKEN Centre for Developmental Biology, Kobe, Japan
Carolynn Dude (PhD awarded May 2008), currently a medical student at the University of Wisconsin, Madison
Hong Xu (PhD awarded May 2008), currently an R&D Manager at COFCO Corporation, China
Dr Kelly Kuan, currently a Molecular & Cell Biologist at Pfizer UK
Ruth McCole, currently a postdoc with Prof Ting Wu, Department of Genetics, Harvard Medical School
Anastasia Seferiadis (MPhil awarded April 2007), currently a Junior Researcher in the Department of Biology and Society, Vrije Universiteit, Amsterdam
Umut Dursun (PhD awarded February 2012)
Jim Blundell (PhD awarded June 2012), currently a graduate medical student at the University of Oxford
Dr Andrew Gillis, currently an NSERC postdoctoral fellow with Prof. Brian Hall, Dalhousie University, Canada (webpage)
Dorit Hockman (PhD awarded February 2014), currently a Junior Research Fellow at Trinity College, University of Oxford

Former rotation students (Wellcome Trust 4-year PhD Programme in Developmental Biology)
Philippe Loiseau, Will Mifsud, Vincent Pasque, Maarten Zwart, Dorit Hockman, Jonathan Lawson, Alexis Hazbun, Tomoki Otani, Leo Otsuki, Marcia Kishida, Surangi Perera

Former rotation students (BBSRC Doctoral Training Partnerships Programme)
Laura-Nadine Schumacher

Former undergraduate research project students
Eleanor Bates, Katie Birley, Jason George, Harry Gibson, Haseeb Rahman, Luke Tyson, Jiexin Zheng, Rob Walsh, Nicola Xiang, Fern Adams, Sophie Miller, Adam Hunt, Natalia Deja, Olivia Burke, Emmy Tsang, Jamie Ladbrooke, Arvind Kumar

Nuffied Undergraduate Research Bursaries in Science
Summer 2010: Sophie Miller, University of Cambridge

Nuffield Science Bursary - Schools and Colleges
Summer 2009: Susannah Worster, Hills Road Sixth Form College, Cambridge
Summer 2010: Andrew Gvozdanovic, The Leventhorpe School, Sawbridgeworth, Herts.
Summer 2011: Danielle Lis, Saffron Walden County High School, Essex

Amgen Scholars Programme, University of Cambridge
Summer 2011: Patrick Kennedy (University of Oxford)

Sources of funding: BBSRC, Leverhulme Trust, March of Dimes (Basil O'Connor Starter Scholar Award), Isaac Newton Trust, Wellcome Trust

Main Collaborators
Professor Marianne Bronner-Fraser, California Institute of Technology, USA
Dr Alan Burns, UCL Institute of Child Health, London
Dr Marcus Davis, Kennesaw State University, USA
Dr Raj Ladher, RIKEN Centre for Developmental Biology, Kobe, Japan
Dr Sylvie Mazan, Station Biologique, Roscoff, France
Dr Filippo Rijli, Friedrich Miescher Institute for Biomedical Research, Basel, Switzerland
Dr Andrea Streit, King's College London
Professor Eric Turner, Seattle Children's Research Institute, USA

External Teaching: I lecture on the summer Embryology Course for advanced graduate students and postdocs at the Marine Biological Laboratory, Woods Hole, Massachusetts.

Selected Publications
Piotrowski, T. and Baker, C.V.H., 2014. The development of lateral line placodes: Taking a broader view. Dev. Biol. 389, 68-81. (ref.)

Modrell, M.S., Hockman, D., Uy, B., Buckley, D., Sauka-Spengler, T., Bronner, M.E., Baker, C.V.H. (2014) A fate-map for cranial sensory ganglia in the sea lamprey. Dev. Biol. 385, 405-416. (ref.)

Barraud, P., St John, J. A., Stolt, C. C., Wegner, M. and Baker, C. V. H. (2013). Olfactory ensheathing glia are required for embryonic olfactory axon targeting and the migration of gonadotropin-releasing hormone neurons. Biol. Open 2, 750-759 (ref.)

Gillis, J. A.*, Modrell, M. S. and Baker, C. V. H. (2013). Developmental evidence for serial homology of the vertebrate jaw and gill arch skeleton. Nature Communications 4, 1436. doi: 10.1038/ncomms2429 (ref.) *Corresponding author.

O'Neill, P., Mak, S.-S., Fritzsch, B., Ladher, R. K.* and Baker, C. V. H.* (2012). The amniote paratympanic organ develops from a previously undiscovered sensory placode. Nature Communications 3, 1041. doi:10.1038/ncomms2036 (ref.) *Joint corresponding authors.

Gillis, J. A., Modrell, M. S., Northcutt, R. G., Catania, K. C., Luer, C. A. and Baker, C. V. H. (2012) Electrosensory ampullary organs are derived from lateral line placodes in cartilaginous fishes. Development 139, 3142-3146. (ref.)

Modrell, M. S. and Baker, C. V. H. (2012) Evolution of electrosensory ampullary organs: conservation of Eya4 expression during lateral line development in jawed vertebrates. Evol. Dev. 14, 277-285 (ref.)

Sabado, V., Barraud, P., Baker, C. V. H. and Streit, A. (2012) Specification of GnRH-1 neurons by antagonistic FGF and retinoic acid signalling. Dev. Biol. 362: 254-262 (ref.)

Modrell, M. S., Bemis, W. E., Northcutt, R. G., Davis, M. C. and Baker, C. V. H. (2011) Electrosensory ampullary organs are derived from lateral line placodes in bony fishes. Nature Communications 2: 496, DOI:10.1038/ncomms1502) (ref.)

Gillis, J. A.*, Rawlinson, K. A., Bell, J., Lyon, W. S., Baker, C. V. H. and Shubin N. H.* (2011) Holocephalan embryos provide evidence for gill arch appendage reduction and opercular evolution in cartilaginous fishes. Proc. Natl. Acad. Sci. U.S.A. 108: 1507-12 (ref.) *Joint corresponding authors.

Modrell, M. S., Buckley, D. and Baker, C. V. H.* (2011) Molecular analysis of neurogenic placode development in a basal ray-finned fish. Genesis 49: 278-94 (ref.)

Barraud P., Seferiadis A. A., Tyson L. D., Zwart M. F., Szabo-Rogers H. L., Ruhrberg C., Liu K. J., Baker C. V. H.* (2010) Neural crest origin of olfactory ensheathing glia. Proc. Natl. Acad. Sci. U.S.A. 107: 21040-5 (ref.)

Dude, C. M., Kuan, C.-Y. K., Bradshaw, J. R., Greene, N. D. E., Relaix, F., Stark, M. R.*, Baker, C. V. H.* (2009). Activation of Pax3 target genes is necessary but not sufficient for neurogenesis in the ophthalmic trigeminal placode. Dev. Biol. 326: 314-26 (ref.) *Joint corresponding authors

Baker, C. V. H. (2008) The evolution and elaboration of vertebrate neural crest cells. Curr. Op. Gen. Dev. 18: 536-43 (ref.)

Baker, C. V. H., O'Neill, P. and McCole, R. B. (2008) Lateral line, otic and epibranchial placodes: developmental and evolutionary links? J. Exp. Zool. B Mol. Dev. Evol. 310B: 370-383 (ref.)

Xu, H., Dude, C. M. and Baker, C. V. H. (2008) Fine-grained fate maps for the ophthalmic and maxillomandibular trigeminal placodes in the chick embryo. Dev. Biol. 317:174-86 (ref.)

Lassiter, R. N., Dude, C. M., Reynolds, S. B., Winters, N. I., Baker, C. V. H., and Stark, M. R. (2007). Canonical Wnt signaling is required for ophthalmic trigeminal placode cell fate determination and maintenance. Dev. Biol. 308: 392-406 (ref.)

O'Neill, P., McCole, R. B. and Baker, C. V. H. (2007) A molecular analysis of neurogenic placode and cranial sensory ganglion development in the shark, Scyliorhinus canicula. Dev. Biol. 304: 156-181 (ref.)

Baker, C. V. H. and Schlosser, G. (2005) Editorial: the evolutionary origin of neural crest and placodes. J. Exp. Zool. B Mol. Dev. Evol. 304: 269-273 (ref.)

Lee, V. M., Bronner-Fraser, M. and Baker, C. V. H. (2005) Restricted response of mesencephalic neural crest to sympathetic differentiation signals in the trunk. Dev. Biol. 278: 175-192 (ref.)

Baker, C. V. H., Stark, M. R. and Bronner-Fraser, M. (2002). Pax3-expressing trigeminal placode cells can localize to trunk neural crest sites but are committed to a cutaneous sensory neuron fate. Dev. Biol. 249, 219-236 (ref.)

Baker, C. V. H. and Bronner-Fraser, M. (2001) Vertebrate cranial placodes. Part I. Embryonic induction. Dev. Biol. 232: 1-61 (ref.)

Baker, C. V. H. and Bronner-Fraser, M. (2000) Establishing neuronal identity in vertebrate neurogenic placodes. Development 127: 3045-3056 (ref.)

Baker, C. V. H.*, Stark, M. R.*, Marcelle, C. and Bronner-Fraser, M. (1999) Competence, specification and induction of Pax-3 in the trigeminal placode. Development 126: 147-156 (ref.) *Joint first authors.

Baker, C. V. H., Bronner-Fraser, M., Le Douarin, N. M. and Teillet, M.-A. (1997) Early- and late-migrating cranial neural crest cell populations have equivalent developmental potential in vivo. Development 124: 3077-3087 (ref.)

Baker, C. V. H. and Bronner-Fraser, M. (1997) The origins of the neural crest. Part I: Embryonic induction. Mech. Dev. 69: 3-11 (ref.)

Baker, C. V. H. and Bronner-Fraser, M. (1997) The origins of the neural crest. Part II: An evolutionary perspective. Mech. Dev. 69: 13-29 (ref.)

Baker, C. V. H., Sharpe, C. R., Torpey, N. P., Heasman, J. and Wylie, C. C. (1995) A Xenopus c-kit-related receptor tyrosine kinase expressed in migrating stem cells of the lateral line system. Mech. Dev. 50: 217-228 (ref.)

Book Chapters
Baker, C. V. H. (2005) Neural Crest and Cranial Ectodermal Placodes. In "Developmental Neurobiology", 4th edition (M. S. Rao and M. Jacobson, Eds.), pp. 67-127. Springer, New York.

Baker, C. V. H. (2005). The Embryology of Vagal Sensory Neurons. In "Advances in Vagal Afferent Neurobiology" (B. J. Undem and D. Weinreich, Eds.), pp. 3-26. CRC Press, Boca Raton.

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Above: Cross-section of the embryonic chicken olfactory bulb showing neural crest-derived olfactory ensheathing cells (green). (Blue, axons; red, low-affinity neurotrophin receptor.) Dr Perrine Barraud


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Above: Head of a paddlefish (Polyodon) embryo stained for Sytox green, showing fields of rosette-like ampullary organs (containing electroreceptors) on either side of lines of mechanosensory hair cells. Dr Melinda Modrell


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Above: Scanning electron micrograph of a frog (Xenopus) mechanosensory lateral line organ showing the long kinocilia of the mechanosensory hair cells that make up the neuromast. The kinocilia are deflected by water movements. Dr Clare Baker & Dr Jeremy Skepper


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Above: Neurons (red) in the developing trigeminal ganglion derive from two distinct placodes and the neural crest. Only the ophthalmic trigeminal placode-derived neurons (top) express Pax3 (green). The non-neuronal Pax3-positive cells are neural crest cells. Dr Clare Baker


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Above: Section showing sensory neurons (red nuclei; blue axons) formed by an epibranchial placode (thickened surface ectoderm), which expresses Pax2 (green nuclei). Dr Paul O'Neill


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Above: A holocephalan (elephant fish) embryo, showing expression of the Sonic hedgehog gene (dark purple staining) in the developing operculum and gill arches. Dr Andrew Gillis