Theses

Carolyn Marks


“Regulatory mechanisms in olfactory system assembly and function”
7 December 2012

Abstract from KI website

External examiner:
Prof. Charles Greer
Yale University,
New Haven, CT
USA

This thesis is based on the following papers:

I. Nguyen MQ, Zhou Z, Marks CA, Ryba NJ, Belluscio L. Prominent roles for odorant receptor coding sequences in allelic exclusion. Cell 2007 Nov 30;131(5):1009-17 [Abstract]

II. Nguyen MQ, Marks CA, Belluscio L, Ryba NJ. Early expression of odorant receptors distorts the olfactory circuitry. J Neurosci. 2010 Jul 7;30(27):9271-9 [Abstract]

III. Marks CA, Cheng K, Cummings DM, Belluscio L. Activity-dependent plasticity in the olfactory intrabulbar map. J Neurosci. 2006 Nov 1;26(44):11257-66 [Abstract]

IV. Marks, CA, Belluscio L, Ibanez CF. Critical role of GFRa1 in the development and function of the mouse olfactory system. J. Neurosci. 2012, Nov 28;32 (48): 17306-17320 [PDF]

V. Marks CA, Belluscio L, Ibanez CF. A cell-autonomous role of GFRa1 in the development of olfactory bulb GABAergic interneurons. Manuscript

Maurice Perrinjaquet


“Control of neuronal survival, migration and outgrowth by GDNF and its receptors”
16 December, 2010

Abstract from KI website

External examiner:
Rosalind Segal
Departments of Neurobiology, Cancer Biology and Pediatric Oncology
Harvard Medical School and Dana-Farber Cancer Institute
Boston, MA, USA

This thesis is based on the following papers:

I. Perrinjaquet, M., Vilar, M. and Ibanez, C.F. (2010) Protein-tyrosine phosphatase SHP2 contributes to GDNF neurotrophic activity through direct binding to phospho-Tyr687 in the RET receptor tyrosine kinase. J. Biol. Chem. 285, 31867-31875. [PDF]

II. Perrinjaquet, M., Sjostrand, D., Moliner, A., Zechel, S., Lambelle, F., Maina, F. and Ibanez, C.F. (2010). Met signaling in GABAergic neurons of the medial ganglionic eminence restricts GDNF activities in cells expressing GFRa1 and a novel transmembrane receptor. Manuscript. Later published in 2011: J. Cell Sci., 124, 2797-2805. [PDF]

III. Kjaer, S., Kurokawa, K., Perrinjaquet, M., Abrescia, C., and Ibanez, C.F. (2006) Self-association of the transmembrane domain of RET underlines oncogenic activation by MEN2A mutattions. Oncogene 25, 7086-7095. [PDF]

Dan Sjostrand


“GDNF and its receptors : A structure-function analysis of the NCAM-GDNF-GFRa1 complex and an examination of potential receptor candidates”
22 May, 2008

Abstract from KI website

External examiner:
Rudiger Klein
Max Planck Institute of Neurobiology
Martinsried, Germany

This thesis is based on the following papers:

I. Sjostrand, D., Carlsson, J., Paratcha, G,. Persson, B. and Ibanez, C.F. (2007) Disruption of the GDNF binding site in NCAM dissociates ligand binding and homophilic cell adhesion. J. Biol. Chem., 282, 12734-12740.[PDF]

II. Sjostrand and Ibanez, C.F. (2008) Insights into GFRa1 Regulation of Neural Cell Adhesion Molecule (NCAM) Function from Structure-Function Analysis of the NCAM/GFRa1 Receptor . J. Biol. Chem., 283, 13792 -13798.[PDF]

III. Abrescia, C., Sjostrand, D., Kjaer, S. and Ibanez, C.F. (2005) Drosophila RET contains an active tyrosine kinase and elicits neurotrophic activities in mammalian cells. FEBS Lett. 579, 3789-3796. [PDF]

IV. Sjostrand, D., Moliner, A. and Ibanez, C.F. (2008) GDNF signaling in GABAergic neurons of the medial ganglionic eminence: Roles of Met and ErbB4. Manuscript. Later published in 2011: J. Cell Sci., 124, 2797-2805. [PDF]

Olov Andersson


“Genetic analysis of ligand-recpetor interactions in the TGF-b superfamily during early embryonic development”
01 December, 2006

Abstract from KI website

External examiner:
Se-Jin Lee
Dept. of Molecular Biology and Genetics
Johns Hopkins University School of Medicine
Baltimore, USA

This thesis is based on the following papers:

I. Reissmann, E., Jornvall, H., Blokzijl, A., Andersson, O., Chang, C., Minchiotti, G., Persico, M., Ibanez, C. F., and Brivanlou, A. H. (2001) The orphan receptor ALK7 and the Activin receptor ALK4 mediate signaling by Nodal proteins during vertebrate development.Genes & Dev. 15, 2010-2022. *Equal contribution. [PDF]

II. Jornvall, H., Reissmann, E., Andersson, O., Mehrkash, M. and Ibanez, C.F. (2004) ALK7, a receptor for Nodal, is dispensable for embryogenesis and left-right patterning in the mouse. Mol. Cell. Biol., 24, 9383-9389. [PDF]

III. Andersson, O., Reissmann, E., Jornvall, H. and Ibanez, C.F. (2006) Synergistic interaction between Gdf1 and Nodal during anterior axis development. Dev. Biol., 293, 370-381. [PDF]

IV. Andersson, O., Reissmann, E. and Ibanez, C.F. (2006) Growth differentiation factor 11 signals through the transforming growth factorbeta receptor ALK5 to regionalize the anterior-posterior axis. EMBO Rep., 7, 831-837. [PDF]

V. Andersson O, Ibanez CF. (2006) Distinct and cooperative roles of mammalian Vg1 homologs GDF1 and GDF3 during embryonic patterning. Manuscript. Later published in Dev. Biol., 311, 500-511. [PDF]

Andries Blokzijl


“Ligand-receptor interactions and signaling crosstalk in the TGF-b superfamily”
21 February, 2003

Abstract from KI website

External examiner:
Caroline Hill
Cancer Research UK
London, UK

This thesis is based on the following papers:

I. Jornvall, H., Blokzijl, A., ten Dijke, P., and Ibanez, C. F. (2001) The orphan receptor serine/threonine kinase ALK7 signals arrest of proliferation and morphological differentiation in a neuronal cell line. J. Biol. Chem. 276, 5140-5146. [PDF]

II. Reissmann, E., Jornvall, H.*, Blokzijl, A.*, Andersson, O., Chang, C., Minchiotti, G., Persico, M., Ibanez, C. F., and Brivanlou, A. H. (2001) The orphan receptor ALK7 and the Activin receptor ALK4 mediate signaling by Nodal proteins during vertebrate development. Genes & Dev. 15, 2010-2022. *Equal contribution. [PDF]

III. Blokzijl, A., ten Dijke, P., and Ibanez, C. F. (2002) Physical and functional interaction between GATA-3 and Smad3 allows TGF-bregulation of GATA target genes. Curr. Biol. 12, 35-45. [PDF]

IV. Blokzijl, A., Reissmann, E., and Ibanez, C. F. (2003) Physical and functional interactions between Smad proteins and Phox2 homeodomain transcription factors. Manuscript.

V. Blokzijl, A., Dahlqvist, C., Reissmann, E., Falk, A., Moliner, A., Lendahl, U., and Ibanez, C. F. (2003) Crosstalk between the Notch and TGF-b signaling pathways mediated by interaction of the Notch intracellular domain with Smad3. Manuscript. Later published in 2003: J. Cell Biol. 163, 723-728. [PDF]

Susanna Eketjall


“Structure function studies of GDNF and other members of the TGF-b superfamily”
12 November, 2002

Abstract from KI website

External examiner:
Mart Saarma
University of Helsinki
Helsinki, Finland

This thesis is based on the following papers:

I. Eketjall, S., Fainzilber, M., Murray-Rust, J., and Ibanez, C.F. (1999) Distinct structural elements in GDNF mediate binding to the GFRa1 and activation of the GFRa1-c-Ret receptor complex. EMBO J. 18, 5901-5910. [PDF]

II. Eketjall, S. and Ibanez C.F. (2002) Functional characterization of mutations in the GDNF gene of patients with Hirschsprung disease.Hum. Mol. Gen. 11, 325-329. [PDF]

III. Scott, R.P., Eketjall, S., Aineskog, H., and Ibanez, C.F. (2002) Distinct signaling mechanisms by isoforms of the Ret kinase receptor are mediated through differential interaction with Cbl and CrkL. Manuscript. Later published in 2005, J. Biol. Chem.: in press. [PDF]

IV. Eketjall, S., Jornvall, H., Lonnerberg, P., Kobayashi, S., and Ibanez, C.F. (2002) Recent Evolutionary Origin within the Primate Lineage of two Genes with Similarity to Members of the TGF-b Superfamily Specifically Expressed in the Nervous System. Manuscript. Later published in 2004: Cell. Mol. Life Sci., 61, 488-496. [PDF]

Rizaldy Scott


“Signal transduction mechanisms mediated by the GDNF family of ligands and their receptors”
8 November, 2002

External examiner:
Marc Billaud
Universite Claude Bernard Lyon 1
Lyon, France

This thesis is based on the following papers:

I. Scott, R. P. and Ibanez, C. F. (2001) Determinants of ligand binding specificity in the GDNF family receptor alphas (GFRas). J. Biol. Chem.276, 1450-1458. [PDF]

II. Scott, R. P., Cederlund, E., Bergmann and Ibanez, C. F. (2002) Structural characterization of GFRas: Identification of ligand binding epitopes, and mapping of disulfide bridges and glycosylation sites. Manuscript. [PDF]

III. Trupp, M.*, Scott, R. P.*, Whittemore, S. R., and Ibanez, C. F. (1999) Ret-dependent and -independent mechanisms of GDNF signalling in neuronal cells. J. Biol. Chem. 274, 20885-20894. *Shared first authorship. [PDF]

IV. Besset, V., Scott, R. P. and Ibanez, C. F. (2000). Signaling complexes and protein-protein interactions involved in the activation of the Ras and PI3K pathways by the c-Ret receptor tyrosine kinase. J. Biol. Chem. 275, 39159-39166. [PDF]

V. Scott, R.P., Eketjall, S., Aineskog, H. and Ibanez, C.F. (2002) Distinct signaling mechanisms by isoforms of the Ret kinase receptor are mediated through differential interaction with Cbl and CrkL. Manuscript. Later published in 2005: J. Biol. Chem.280, 13442-13449. [PDF]

VI. Scott, R. P., Murray-Rust, J., McDonald, N. and Ibanez, C. F. (2002) Production, purification, crystallization of the kinase domain of c-Ret and its oncogenic variants. Manuscript.

Henrik Jornvall


“Functional and bioinformatical studies of the TGF-b superfamily: Identification and characterization of ALK7”
23 November, 2001

Abstract from KI website

External examiner:
Urban Lendahl
Karolinska Institute
Stockholm, Sweden

This thesis is based on the following papers:

I. Ryden, M., Imamura, T., Jornvall, H., Belluardo, N., Neveu, I., Trupp, M., Okadome, T., ten Dijke, P., Ibanez, C.F. (1996) A novel type I receptor serine-threonine kinase predominantly expressed in the adult central nervous system. J. Biol. Chem. 271, 30603-30609. [PDF]

II. Jornvall, H., Blokzijl, A., ten Dijke, P., Ibanez, C.F. (2001) The orphan receptor serine/threonine kinase ALK7 signals arrest of proliferation and morphological differentiation in a neuronal cell line. J. Biol. Chem. 276, 5140-5146. [PDF]

III. Reissmann, E., Jornvall, H., Blokzijl, A., Andersson, O., Chang, C., Minchiotti, G., Persico, M.G., Ibanez, C.F., Brivanlou, A.H. (2001) The orphan receptor ALK7 and the activin receptor ALK4 mediate signaling by nodal proteins during vertebrate development. Genes & Dev. 15, 2010-2022. [PDF]

IV. Jornvall, H., Ibanez, C.F. (2001) Targeted deletion of the receptor serine/threonine kinase ALK7 in mice. Manuscript. Later published in Mol. Cell. Biol. 24, 9383-9389. [PDF]

V. Jornvall, H. (1999) Motifer, a search tool for finding amino acid sequence patterns from nucleotide sequence databases. FEBS Lett. 456, 85-88. [PDF]

VI. Jornvall, H., Eketjall, S., Gustavsson, J., Kobayashi, S., Lonnerberg, P., Ibanez, C.F. (2001) Identification of two new members of the TGFb ligand superfamily and a new member of the GFRa receptor family using a bioinformatics tool. Manuscript. Later published in 2004: Cell Mol Life Sci61, 488-496. [PDF]

Thomas Ringstedt


“Neurothrophins during development : Overexpression in neural stem cells”
5 June, 1998

Abstract from KI website

External examiner:
Gary R. Lewin
Max-Delbruck Center for Molecular Medicine
Berlin, Germany

This thesis is based on the following papers:

I. Ringstedt, T., Lagercrantz, H., Persson, H. (1993) Expression of members of the trk family in the developing postnatal rat brain. Dev. Brain Res. 72, 119-131. [PubMed]

II. Ringstedt, T., Linnarsson, S., Wagner, J., Lendahl, U., Kokaia, Z., Arenas, E., Ernfors, P., and Ibanez, C. F. (1998). BDNF regulates reelin expression and cajal-retzius cell development in the cerebral cortex. Manuscript. Later published in 1998, Neuron 21, 305-315. [PDF]

III. Ringstedt, T., Kucera, J., Lendahl, U., Ernfors, P., and Ibanez, C. F. (1997). Limb proprioceptive deficits without neuronal loss in transgenic mice overexpressing neurotrophin-3 in the developing nervous system. Development 124, 2603-2613. [PDF]

IV. Ringstedt, T., Ibanez, C. F., and Nosrat, C. (1998). Role of BDNF in target invasion in the gustatory system. Manuscript. Later published in 1999, J. Neurosci. 19, 3507-3518. [PDF]

V. Ringstedt, T., Tang, L.Q., Persson, H., Lendahl, U., Lagercrantz, H. (1995) Expression of c-fos, tyrosine hydroxylase, and neuropeptide mRNA in the rat brain around birth: effects of hypoxia and hypothermia. Pediatr Res. 1995 Jan;37(1):15-20. [PubMed]

Miles Trupp


“Neurotrophic signalling by GDNF and its receptors”
2 June, 1998

Abstract from KI website

External examiner:
Michael E. Greenberg
Harvard Medical School
Cambridge, USA

This thesis is based on the following papers:

I. Trupp, M., Ryden, M., Jornvall, H., Timmusk, T., Funakoshi, H., Arenas, E., and Ibanez, C. F. (1995). Peripheral expression and biological activities of GDNF, a new neurotrophic factor for avian and mammalian peripheral neurons. J. Cell. Biol. 130, 137-148 [PDF]

II. Arenas, E., Trupp, M., Akerud, P., and Ibanez, C. F. (1995). GDNF prevents degeneration and promotes the phenotype of brain noradrenergic neurons in vivo. Neuron 15, 1465-1473 [PDF]

III. Trupp, M., Arenas, E., Fainzilber, M., Nilsson, A.-S., Sieber, B. A., Grigoriou, M., Kilkenny, C., Salazar-Grueso, E., Pachnis, V., Arumae, U., Sariola, H., Saarma, M., and Ibanez, C. F. (1996). Functional receptor for glial cell line-derived neurotrophic factor encoded by the c-ret proto-oncogene product. Nature 381, 785-789 [PDF]

IV. Trupp, M., Belluardo, N., Funakoshi, H., and Ibanez, C. F. (1997). Complementary and overlapping expression of glial cell line-derived neurotrophic factor (GDNF), c-ret proto-oncogene, and gdnf receptor-alpha indicates multiple mechanisms of trophic actions in the adult rat CNS. J. Neurosci. 17, 3554-3567 [PDF]

V. Trupp, M., Raynoschek, C., Belluardo, N., and Ibanez, C. F. (1998). Multiple GPI-anchored receptors control GDNF-dependent and independent activation of the c-Ret receptor tyrosine kinase. Mol. Cell. Neurosci. 11, 47-63 [PDF]

VI. Trupp, M., Scott, R., Whittemore, S. R., and Ibanez, C. F. (1998). Ret-dependent and -independent mechanisms of GDNF signalling in neuronal cells. Manuscript. Later published in 1999, J. Biol. Chem. 274, 20885-20894 [PDF]

Peter Lonnerberg


“Mechanisms of cell type-specific gene transcription : Studies on the choline acetyltransferase gene”
27 May, 1998

Abstract from KI website

External examiner:
Thomas Perlmann
Ludwig Institue for Cancer Research
Stockholm, Sweden

This thesis is based on the following papers:

I. Lonnerberg, P., Schoenherr, C. J., Anderson, D. J., and Ibanez, C. F. (1996) Cell-specific regulation of the choline acetyltransferase gene: Role of the neuron-restrictive silencer element and cholinergic-specific enhancer sequences. J. Biol. Chem. 271, 33358-33365. [PDF]

II. Lonnerberg, P., Lendhal, U., Funakoshi, H., Arhlund-Richter, L., Persson, H., and Ibanez, C. F. (1995) Regulatory region in choline acetyltransferase gene directs developmental and tissue specific expression in transgenic mice. Proc. Natl. Acad. Sci. USA 92, 4046-4050. [PDF]

III. Lonnerberg, P. and Ibanez, C. F. (1998) Inducible and tissue-specific gene targeting to cholinergic neurons. Manuscript. [PDF]

IV. Lonnerberg, P., and Ibanez, C. F. (1998) Novel, testis-specific mRNA transcripts encoding N-terminally truncated choline acetyltransferase.Manuscript. Later published in 1999, Mol. Reprod. Dev. 53, 274-281. [PDF]

V. Lonnerberg P, Soder O, Parvinen M, Ritzen EM, Persson H. (1992) Beta-nerve growth factor influences the expression of androgen-binding protein messenger ribonucleic acid in the rat testis. Biol. Reprod. 47, 381-388. [PubMed]

VI. Lonnerberg P, Parvinen M, Jahnsen T, Hansson V, Persson H. (1992) Stage- and cell-specific expression of cyclic adenosine 3′,5′-monophosphate-dependent protein kinases in rat seminiferous epithelium. Biol. Reprod. 46, 1057-1068. [PubMed]

Leopold Ilag


“Biochemical and biophysical aspects of molecular recognition and signalling by neurotrophins”
7 November, 1997

Abstract from KI website

External examiner:
Ralph Bradshaw
University of California Irvine
Irvine, USA

This thesis is based on the following papers:

I. Ilag, L.L., Lonnerberg, P. Persson, H. and Ibanez, C.F. (1994) Role of a variable b-hairpin loop in determining biological specificities in neurotrophin family. J. Biol. Chem. 269: 19941-19946. [PDF]

II. Ibanez, C.F., Ilag, L.L., Murray-Rust, J. and Persson, H. (1993) An extended surface of binding to Trk tyrosine kinase receptors in NGF and BDNF allows the engineering of a multifunctional pan-neurotrophin. EMBO J. 12: 2281-2293. [PDF]

III. Ilag, L.L., Curtis, R., Glass, D., Funakoshi, H., Tobkes, N., Ryan, T., Acheson, A., Lindsay, R., Persson, H., Yancopoulos, G.D., DiStefano, P., and Ibanez, C.F. (1995) Pan-neurotrophin 1: A genetically engineered neurotrophic factor displaying multiple specificities in peripheral neurons in vitro and in vivo. Proc. Natl. Acad. Sci. USA 92:607-611. [PDF]

IV. Ilag, L.L. and Ibanez, C.F. (1997) Engineering of the heparin-binding domain of neurotrophin-6 onto nerve growth factor. Manuscript. [HTML]

V. Liepinsh, E., Ilag, L.L., Otting, G., and Ibanez, C.F. (1997) NMR structure of the death domain of the p75 neurotrophin receptor. EMBO J. 16: 4999-5005. [PDF]

VI. Ilag, L.L., Rottenberger, C., Liepinsh, E., Ibanez, C.F., Otting, G., and Ilag, L.L. (1997) Selection of a peptide-ligand to the p75 neurotrophin receptor death domain and determination of its binding site by NMR. Manuscript. Later published in 1999 in Biochem. Biophys. Res. Comm.255, 104-109. [PDF]

Mikael Ryden


“Neurotrophic factors and their receptors: Structure-function relationships and signalling mechanisms”
25 April, 1997

Abstract from KI website

External examiner:
Carl-Henrik Heldin
Ludwig Institute for Cancer Research
Uppsala, Sweden

This thesis is based on the following papers:

I. Ryden, M., Murray-Rust, J., Glass, D., Ilag, L.L., Trupp, M., Yancopoulos, G.D., McDonald, N.Q. and Ibanez, C.F. (1995) Functional analysis of mutant neurotrophins deficient in low-affinity binding reveals a role for p75LNGFR in NT-4 signalling. EMBO J., 14, 1979-1990. [PDF]

II. Ryden, M. and Ibanez, C.F. (1996) Binding of neurotrophin-3 to p75LNGFR, TrkA and TrkB mediated by a single functional epitope distinct from that recognized by TrkC. J. Biol. Chem., 271, 5623-5637 [PDF]

III. Ryden, M., Hempstead, B. and Ibanez, C.F. (1997) Differential modulation of neuron survival during development by nerve growth factor binding to the p75 neurotrophin receptor. Manuscript. Later published in 1997, J. Bio.l Chem., 272, 16322-16328 [PDF]

IV. Ryden, M. and Ibanez, C.F. (1997) A second determinant of binding to the p75 neurotrophin receptor revealed by alanine-scanning mutagenesis of a conserved loop in NGF. Manuscript. Later published in 1997, J. Bio.l Chem., 272, 33085-33091 [PDF]

V. Ryden, M., Sehgal, R., Dominici, C., Schilling, F.H., Ibanez, C.F., Kogner, P. (1996) Br. J. Cancer 74, 773-779 [PubMed]

VI. Ryden, R., Imamura, T., Jornvall, H., Neveu, I., Trupp, M., Belluardo, N., Okadome, T., ten Dijke, P., and Ibanez, C. F. (1996). A novel type I serine-threonine kinase receptor predominantly expressed in the adult central nervous system. J. Biol. Chem. 271, 30603-30609 [PDF]