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Hallböök, Finn
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Publications (10 of 97) Show all publications
Brusini, I., Carneiro, M., Wang, C., Rubin, C.-J., Ring, H., Afonso, S., . . . Andersson, L. (2018). Changes in brain architecture are consistent with altered fear processing in domestic rabbits. Proceedings of the National Academy of Sciences of the United States of America, 115(28), 7380-7385
Open this publication in new window or tab >>Changes in brain architecture are consistent with altered fear processing in domestic rabbits
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2018 (English)In: Proceedings of the National Academy of Sciences of the United States of America, ISSN 0027-8424, E-ISSN 1091-6490, Vol. 115, no 28, p. 7380-7385Article in journal (Refereed) Published
Abstract [en]

The most characteristic feature of domestic animals is their change in behavior associated with selection for tameness. Here we show, using high-resolution brain magnetic resonance imaging in wild and domestic rabbits, that domestication reduced amygdala volume and enlarged medial prefrontal cortex volume, supporting that areas driving fear have lost volume while areas modulating negative affect have gained volume during domestication. In contrast to the localized gray matter alterations, white matter anisotropy was reduced in the corona radiata, corpus callosum, and the subcortical white matter. This suggests a compromised white matter structural integrity in projection and association fibers affecting both afferent and efferent neural flow, consistent with reduced neural processing. We propose that compared with their wild ancestors, domestic rabbits are less fearful and have an attenuated flight response because of these changes in brain architecture.

National Category
Psychology Radiology, Nuclear Medicine and Medical Imaging
Identifiers
urn:nbn:se:uu:diva-355452 (URN)10.1073/pnas.1801024115 (DOI)000438050900076 ()29941556 (PubMedID)
Funder
Knut and Alice Wallenberg FoundationSwedish Research CouncilThe Swedish Brain FoundationEuropean Social Fund (ESF)
Available from: 2018-06-29 Created: 2018-06-29 Last updated: 2018-09-25Bibliographically approved
Blixt, M. K. E., Konjusha, D., Ring, H. & Hallböök, F. (2018). Zinc finger gene nolz1 regulates the formation of retinal progenitor cells and suppresses the Lim3/Lhx3 phenotype of retinal bipolar cells in chicken retina. Developmental Dynamics, 247(4), 630-641
Open this publication in new window or tab >>Zinc finger gene nolz1 regulates the formation of retinal progenitor cells and suppresses the Lim3/Lhx3 phenotype of retinal bipolar cells in chicken retina
2018 (English)In: Developmental Dynamics, ISSN 1058-8388, E-ISSN 1097-0177, Vol. 247, no 4, p. 630-641Article in journal (Refereed) Published
Abstract [en]

Background: The zinc-finger transcription factor Nolz1 regulates spinal cord neuron development by interacting with the transcription factors Isl1, Lim1, and Lim3, which are also important for photoreceptors, horizontal and bipolar cells during retinal development. We, therefore, studied Nolz1 during retinal development.

Results: Nolz1 expression was seen in two waves during development: one early (peak at embryonic day 3-4.5) in retinal progenitors and one late (embryonic day 8) in newly differentiated cells in the inner nuclear layer. Overexpression and knockdown showed that Nolz1 decreases proliferation and stimulates cell cycle withdrawal in retinal progenitors with effects on the generation of retinal ganglion cells, photoreceptors, and horizontal cells without triggering apoptosis. Overexpression of Nolz1 gave more p27 positive cells. Sustained overexpression of Nolz1 in the retina gave fewer Lim3/Lhx3 bipolar cells.

Conclusions: We conclude that Nolz1 has multiple functions during development and suggest a mechanism in which Nolz1 initially regulates the proliferation state of the retinal progenitor cells and then acts as a repressor that suppresses the Lim3/Lhx3 bipolar cell phenotype at the time of bipolar cell differentiation.

Place, publisher, year, edition, pages
WILEY, 2018
Keywords
chicken embryo, differentiation, horizontal cells, in ovo electroporation, Isl1, Lim1, morpholino, p27, piggyback, photoreceptors, repressor
National Category
Neurosciences
Identifiers
urn:nbn:se:uu:diva-350726 (URN)10.1002/dvdy.24607 (DOI)000427563200005 ()29139167 (PubMedID)
Funder
Swedish Research Council, MH521.2013.3346]Swedish Childhood Cancer Foundation, PR20150122]
Available from: 2018-05-17 Created: 2018-05-17 Last updated: 2018-05-17Bibliographically approved
Stenfelt, S., Blixt, M. K. E., All-Ericsson, C., Hallböök, F. & Boije, H. (2017). Heterogeneity in retinoblastoma: a tale of molecules and models. CLINICAL AND TRANSLATIONAL MEDICINE, 6, Article ID 42.
Open this publication in new window or tab >>Heterogeneity in retinoblastoma: a tale of molecules and models
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2017 (English)In: CLINICAL AND TRANSLATIONAL MEDICINE, ISSN 2001-1326, Vol. 6, article id 42Article, review/survey (Refereed) Published
Abstract [en]

Retinoblastoma, an intraocular pediatric cancer, develops in the embryonic retina following biallelic loss of RB1. However, there is a wide range of genetic and epigenetic changes that can affect RB1 resulting in different clinical outcomes. In addition, other transformations, such as MYCN amplification, generate particularly aggressive tumors, which may or may not be RB1 independent. Recognizing the cellular characteristics required for tumor development, by identifying the elusive cell-of-origin for retinoblastoma, would help us understand the development of these tumors. In this review we summarize the heterogeneity reported in retinoblastoma on a molecular, cellular and tissue level. We also discuss the challenging heterogeneity in current retinoblastoma models and suggest future platforms that could contribute to improved understanding of tumor initiation, progression and metastasis in retinoblastoma, which may ultimately lead to more patient-specific treatments.

Place, publisher, year, edition, pages
BIOMED CENTRAL LTD, 2017
Keywords
Cancer, Cell-of-origin, Genetics, Horizontal cells, MYCN, Photoreceptors, OTX2, RB1
National Category
Cancer and Oncology
Identifiers
urn:nbn:se:uu:diva-346610 (URN)10.1186/s40169-017-0173-2 (DOI)000414747600001 ()
Available from: 2018-03-22 Created: 2018-03-22 Last updated: 2018-03-22Bibliographically approved
Thalmann, D. S., Ring, H., Sundström, E., Cao, X., Larsson, M., Kerje, S., . . . Andersson, L. (2017). The evolution of Sex-linked barring alleles in chickens involves both regulatory and coding changes in CDKN2A. PLoS Genetics, 13(4), Article ID e1006665.
Open this publication in new window or tab >>The evolution of Sex-linked barring alleles in chickens involves both regulatory and coding changes in CDKN2A
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2017 (English)In: PLoS Genetics, ISSN 1553-7390, E-ISSN 1553-7404, Vol. 13, no 4, article id e1006665Article in journal (Refereed) Published
Abstract [en]

Sex-linked barring is a fascinating plumage pattern in chickens recently shown to be associated with two non-coding and two missense mutations affecting the ARF transcript at the CDKN2A tumor suppressor locus. It however remained a mystery whether all four mutations are indeed causative and how they contribute to the barring phenotype. Here, we show that Sex-linked barring is genetically heterogeneous, and that the mutations form three functionally different variant alleles. The B0 allele carries only the two non-coding changes and is associated with the most dilute barring pattern, whereas the B1 and B2 alleles carry both the two non-coding changes and one each of the two missense mutations causing the Sex-linked barring and Sex-linked dilution phenotypes, respectively. The data are consistent with evolution of alleles where the non-coding changes occurred first followed by the two missense mutations that resulted in a phenotype more appealing to humans. We show that one or both of the non-coding changes are cis-regulatory mutations causing a higher CDKN2A expression, whereas the missense mutations reduce the ability of ARF to interact with MDM2. Caspase assays for all genotypes revealed no apoptotic events and our results are consistent with a recent study indicating that the loss of melanocyte progenitors in Sex-linked barring in chicken is caused by premature differentiation and not apoptosis. Our results show that CDKN2A is a major locus driving the differentiation of avian melanocytes in a temporal and spatial manner.

Place, publisher, year, edition, pages
PUBLIC LIBRARY SCIENCE, 2017
Keywords
ARF TUMOR-SUPPRESSOR; GENE-EXPRESSION; LOCUS; MUTATIONS; INK4A/ARF; MELANOMA; GENOME; SENESCENCE; NICHE; CELLS
National Category
Genetics
Identifiers
urn:nbn:se:uu:diva-327066 (URN)10.1371/journal.pgen.1006665 (DOI)000402549200008 ()
Available from: 2017-08-01 Created: 2017-08-01 Last updated: 2018-01-03Bibliographically approved
Blixt, M. & Hallböök, F. (2016). A regulatory sequence from the retinoid X receptor gamma gene directs expression to horizontal cells and photoreceptors in the embryonic chicken retina. Molecular Vision, 22, 1405-1420
Open this publication in new window or tab >>A regulatory sequence from the retinoid X receptor gamma gene directs expression to horizontal cells and photoreceptors in the embryonic chicken retina
2016 (English)In: Molecular Vision, ISSN 1090-0535, E-ISSN 1090-0535, Vol. 22, p. 1405-1420Article in journal (Refereed) Published
Abstract [en]

PURPOSE: Combining techniques of episomal vector gene-specific Cre expression and genomic integration using the piggyBac transposon system enables studies of gene expression-specific cell lineage tracing in the chicken retina. In this work, we aimed to target the retinal horizontal cell progenitors. METHODS: A 208 bp gene regulatory sequence from the chicken retinoid X receptor gammagene (RXRgamma208) was used to drive Cre expression. RXRgamma is expressed in progenitors and photoreceptors during development. The vector was combined with a piggyBac "donor" vector containing a floxed STOP sequence followed by enhanced green fluorescent protein (EGFP), as well as a piggyBac helper vector for efficient integration into the host cell genome. The vectors were introduced into the embryonic chicken retina with in ovo electroporation. Tissue electroporation targets specific developmental time points and in specific structures. RESULTS: Cells that drove Cre expression from the regulatory RXRgamma208 sequence excised the floxed STOP-sequence and expressed GFP. The approach generated a stable lineage with robust expression of GFP in retinal cells that have activated transcription from the RXRgamma208 sequence. Furthermore, GFP was expressed in cells that express horizontal or photoreceptor markers when electroporation was performed between developmental stages 22 and 28. Electroporation of a stage 12 optic cup gave multiple cell types in accordance with RXRgamma gene expression in the early retina. CONCLUSIONS: In this study, we describe an easy, cost-effective, and time-efficient method for testing regulatory sequences in general. More specifically, our results open up the possibility for further studies of the RXRgamma-gene regulatory network governing the formation of photoreceptor and horizontal cells. In addition, the method presents approaches to target the expression of effector genes, such as regulators of cell fate or cell cycle progression, to these cells and their progenitor.

National Category
Developmental Biology
Identifiers
urn:nbn:se:uu:diva-313804 (URN)000393909400001 ()28003731 (PubMedID)
Funder
Swedish Research Council, MH521.2013.3346Swedish Childhood Cancer Foundation
Available from: 2017-01-24 Created: 2017-01-24 Last updated: 2017-11-29Bibliographically approved
Harun-Or-Rashid, M., Konjusha, D., Galindo-Romero, C. & Hallböök, F. (2016). Endothelin B Receptors on Primary Chicken Müller Cells and the Human MIO-M1 Müller Cell Line Activate ERK Signaling via Transactivation of Epidermal Growth Factor Receptors. PLoS ONE, 11(12), Article ID e0167778.
Open this publication in new window or tab >>Endothelin B Receptors on Primary Chicken Müller Cells and the Human MIO-M1 Müller Cell Line Activate ERK Signaling via Transactivation of Epidermal Growth Factor Receptors
2016 (English)In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 11, no 12, article id e0167778Article in journal (Refereed) Published
Abstract [en]

Injury to the eye or retina triggers Muller cells, the major glia cell of the retina, to dedifferentiate and proliferate. In some species they attain retinal progenitor properties and have the capacity to generate new neurons. The epidermal growth factor receptor (EGFR) system and extracellular signal-regulated kinase (ERK) signaling are key regulators of these processes in Muller cells. The extracellular signals that modulate and control these processes are not fully understood. In this work we studied whether endothelin receptor signaling can activate EGFR and ERK signaling in Muller cells. Endothelin expression is robustly upregulated at retinal injury and endothelin receptors have been shown to transactivate EGFRs in other cell types. We analyzed the endothelin signaling system in chicken retina and cultured primary chicken Muller cells as well as the human Muller cell line MIO-M1. The Muller cells were stimulated with receptor agonists and treated with specific blockers to key enzymes in the signaling pathway or with siRNAs. We focused on endothelin receptor mediated transactivation of EGFRs by using western blot analysis, quantitative reverse transcriptase PCR and immunocytochemistry. The results showed that chicken Muller cells and the human Muller cell line MIO-M1 express endothelin receptor B. Stimulation by the endothelin receptor B agonist IRL1620 triggered phosphorylation of ERK1/2 and autophosphorylation of (Y1173) EGFR. The effects could be blocked by Src-kinase inhibitors (PP1, PP2), EGFR-inhibitor (AG1478), EGFR-siRNA and by inhibitors to extracellular matrix metalloproteinases (GM6001), consistent with a Src-kinase mediated endothelin receptor response that engage ligand-dependent and ligand-independent EGFR activation. Our data suggest a mechanism for how injury-induced endothelins, produced in the retina, may modulate the Muller cell responses by Src-mediated transactivation of EGFRs. The data give support to a view in which endothelins among several other functions, serve as an injury-signal that regulate the gliotic response of Muller cells.

National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:uu:diva-312630 (URN)10.1371/journal.pone.0167778 (DOI)000389580900045 ()27930693 (PubMedID)
Funder
Swedish Research Council, M 12187
Available from: 2017-01-26 Created: 2017-01-12 Last updated: 2017-11-29Bibliographically approved
Boije, H., Fard, S. S., Edqvist, P.-H. & Hallböök, F. (2016). Horizontal Cells, the Odd Ones Out in the Retina, Give Insights into Development and Disease. Frontiers in Neuroanatomy, 10, Article ID 77.
Open this publication in new window or tab >>Horizontal Cells, the Odd Ones Out in the Retina, Give Insights into Development and Disease
2016 (English)In: Frontiers in Neuroanatomy, ISSN 1662-5129, E-ISSN 1662-5129, Vol. 10, article id 77Article, review/survey (Refereed) Published
Abstract [en]

Thorough investigation of a neuronal population can help reveal key aspects regarding the nervous system and its development. The retinal horizontal cells have several extraordinary features making them particularly interesting for addressing questions regarding fate assignment and subtype specification. In this review we discuss and summarize data concerning the formation and diversity of horizontal cells, how morphology is correlated to molecular markers, and how fate assignment separates the horizontal lineage from the lineages of other retinal cell types. We discuss the novel and unique features of the final cell cycle of horizontal cell progenitors and how they may relate to retinoblastoma carcinogenesis.

Keywords
cell fate, cell cycle regulation, chicken, development, DNA damage, neuronal subtype, retinoblastoma, zebrafish
National Category
Neurology
Identifiers
urn:nbn:se:uu:diva-301132 (URN)10.3389/fnana.2016.00077 (DOI)000379879400001 ()
Funder
Swedish Research Council
Available from: 2016-08-22 Created: 2016-08-18 Last updated: 2017-11-28Bibliographically approved
Blixt, M. & Hallböök, F. (2016). Lineage tracing of horizontal and photoreceptor cells in the embryonic chicken retina. Paper presented at Annual Meeting of the Association-for-Research-in-Vision-and-Ophthalmology (ARVO), MAY 01-05, 2016, Seattle, WA. Investigative Ophthalmology and Visual Science, 57(12)
Open this publication in new window or tab >>Lineage tracing of horizontal and photoreceptor cells in the embryonic chicken retina
2016 (English)In: Investigative Ophthalmology and Visual Science, ISSN 0146-0404, E-ISSN 1552-5783, Vol. 57, no 12Article in journal, Meeting abstract (Refereed) Published
Place, publisher, year, edition, pages
ASSOC RESEARCH VISION OPHTHALMOLOGY INC, 2016
National Category
Ophthalmology
Identifiers
urn:nbn:se:uu:diva-321043 (URN)000394174004160 ()
Conference
Annual Meeting of the Association-for-Research-in-Vision-and-Ophthalmology (ARVO), MAY 01-05, 2016, Seattle, WA
Available from: 2017-04-28 Created: 2017-04-28 Last updated: 2017-04-28Bibliographically approved
Dorshorst, B., Harun-Or-Rashid, M., Bagherpoor, A. J., Rubin, C.-J., Ashwell, C., Gourichon, D., . . . Andersson, L. (2015). A Genomic Duplication is Associated with Ectopic Eomesodermin Expression in the Embryonic Chicken Comb and Two Duplex-comb Phenotypes. PLOS Genetics, 11(3), Article ID e1004947.
Open this publication in new window or tab >>A Genomic Duplication is Associated with Ectopic Eomesodermin Expression in the Embryonic Chicken Comb and Two Duplex-comb Phenotypes
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2015 (English)In: PLOS Genetics, ISSN 1553-7390, E-ISSN 1553-7404, Vol. 11, no 3, article id e1004947Article in journal (Refereed) Published
Abstract [en]

Duplex-comb (D) is one of three major loci affecting comb morphology in the domestic chicken. Here we show that the two Duplex-comb alleles, V-shaped (D*V) and Buttercup (D*C), are both associated with a 20 Kb tandem duplication containing several conserved putative regulatory elements located 200 Kb upstream of the eomesodermin gene (EOMES). EOMES is a T-box transcription factor that is involved in mesoderm specification during gastrulation. In D*V and D*C chicken embryos we find that EOMES is ectopically expressed in the ectoderm of the comb-developing region as compared to wild-type embryos. The confinement of the ectopic expression of EOMES to the ectoderm is in stark contrast to the causal mechanisms underlying the two other major comb loci in the chicken (Rose-comb and Pea-comb) in which the transcription factors MNR2 and SOX5 are ectopically expressed strictly in the mesenchyme. Interestingly, the causal mutations of all three major comb loci in the chicken are now known to be composed of large-scale structural genomic variants that each result in ectopic expression of transcription factors. The Duplex-comb locus also illustrates the evolution of alleles in domestic animals, which means that alleles evolve by the accumulation of two or more consecutive mutations affecting the phenotype. We do not yet know whether the V-shaped or Buttercup allele correspond to the second mutation that occurred on the haplotype of the original duplication event.

National Category
Medical Genetics
Identifiers
urn:nbn:se:uu:diva-248610 (URN)10.1371/journal.pgen.1004947 (DOI)000352197100002 ()25789773 (PubMedID)
Available from: 2015-04-02 Created: 2015-04-02 Last updated: 2018-01-11Bibliographically approved
Blixt, M. K. E., Shirazi Fard, S., All-Ericsson, C. & Hallböök, F. (2015). Adding another piece to the retinoblastoma puzzle. Cell Death and Disease, 6, Article ID e1957.
Open this publication in new window or tab >>Adding another piece to the retinoblastoma puzzle
2015 (English)In: Cell Death and Disease, ISSN 2041-4889, E-ISSN 2041-4889, Vol. 6, article id e1957Article in journal, Editorial material (Refereed) Published
Place, publisher, year, edition, pages
Nature Publishing Group, 2015
National Category
Medical and Health Sciences Cell and Molecular Biology
Research subject
Neurology
Identifiers
urn:nbn:se:uu:diva-279036 (URN)10.1038/cddis.2015.317 (DOI)000367150100040 ()26512965 (PubMedID)
Available from: 2016-02-28 Created: 2016-02-28 Last updated: 2018-01-10Bibliographically approved
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