umu.sePublications
Change search
CiteExportLink to record
Permanent link

Direct link
Cite
Citation style
  • apa
  • ieee
  • modern-language-association-8th-edition
  • vancouver
  • Other style
More styles
Language
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Other locale
More languages
Output format
  • html
  • text
  • asciidoc
  • rtf
BMP-induced L-Maf regulates subsequent BMP-independent differentiation of primary lens fibre cells
Umeå University, Faculty of Medicine, Umeå Centre for Molecular Medicine (UCMM). (Lena Gunhaga)
Umeå University, Faculty of Medicine, Umeå Centre for Molecular Medicine (UCMM). (Lena Gunhaga)
Umeå University, Faculty of Medicine, Umeå Centre for Molecular Medicine (UCMM). (Lena Gunhaga)
2011 (English)In: Developmental Dynamics, ISSN 1058-8388, E-ISSN 1097-0177, Vol. 240, no 8, 1917-1928 p.Article in journal (Refereed) Published
Abstract [en]

Bone morphogenetic protein (BMP) signals are essential for lens development. However, the temporal requirement of BMP activity during early events of lens development has remained elusive. To investigate this question, we have used gain- and loss-of-function analyses in chick explant and intact embryo assays. Here, we show that BMP activity is both required and sufficient to induce L-Maf expression, whereas the onset of δ-crystallin and initial elongation of primary lens fibre cells are BMP-independent. Moreover, before lens placode formation and L-Maf onset, but not after, prospective lens placodal cells can switch to an olfactory placodal fate in response to decreased BMP activity. In addition, L-Maf is sufficient to up-regulate δ-crystallin independent of BMP signals. Taken together, these results show that before L-Maf induction BMP activity is required for lens specification, whereas after L-Maf up-regulation, the early differentiation of primary lens fibre cells occurs independent of BMP signals.

Place, publisher, year, edition, pages
2011. Vol. 240, no 8, 1917-1928 p.
Keyword [en]
lens, development, lens fibre cells, differentiation, BMP, L-Maf, δ-crystallin, chick
National Category
Developmental Biology Cell and Molecular Biology
Identifiers
URN: urn:nbn:se:umu:diva-51584DOI: 10.1002/dvdy.22692ISI: 000292772400005PubMedID: 21761477OAI: oai:DiVA.org:umu-51584DiVA: diva2:484439
Available from: 2012-01-27 Created: 2012-01-27 Last updated: 2017-12-08Bibliographically approved
In thesis
1. Control of early development of the lens and the retina
Open this publication in new window or tab >>Control of early development of the lens and the retina
2013 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

The nervous system is composed of two separate compartments, the central and the peripheral nervous system. The peripheral nervous system (PNS) composed mainly of sensory organs transmits sensory information to the central nervous system (CNS) comprising the brain and the spinal cord. The CNS then processes this information and modifies the behaviour of the organism appropriately. To understand the functioning of these systems one has to understand how the different cell types belonging to these systems are generated during the course of embryonic development. Using the chick eye with the lens, which arises from the region that gives rise to components of PNS, and the retina, belonging to the CNS, as an embryonic model tissue the following questions were addressed: how do the BMP and the FGF signalling pathways affect developmental processes within the lens and retina? When do retinal cells get specified and how do the lens and the retina interact with each other during early development? These questions were addressed by using a combination of in vitro and in vivo assays in chick embryos. We show in chick that lens cells are committed to a lens identity, concomitant with the up-regulation of the lens specific marker, L-Maf. Before the onset of L-maf, or in the absence of ongoing BMP activity, lens cells switch to an olfactory fate. However, after cells have up-regulated L-Maf, they are no longer dependent upon BMP signaling for the next step of lens primary fiber differentiation, which is characterized by the onset of δ-crystallin. We provide evidence that the FGF signalling pathway is critical for regulating proliferation within the developing lens, while FGF and BMP signals cooperate with each other to regulate cell cycle exit. In addition we have characterized the expression of Equarin restricted to the differentiating population within the lens, and we show that this gene is subject to regulation by both FGF and BMP signalling. In the absence of FGF and BMP signals, Equarin expression is down-regulated similar to down-regulation of the cell cycle exit marker p27kip1. Over activation of BMP, but not FGF signals is sufficient to up-regulate Equarin expression within the lens. Concerning retinal cells, we provide evidence that retinal cells are not specified until stage 13 in chick. Prior to stage 13, retinal cells are initially specified as telencephalic cells. Our results indicate that prospective retinal cells require either BMP signals or lens tissue, to maintain a retinal identity and to promote further development of retinal cells.

Place, publisher, year, edition, pages
Umeå: Umeå universitet, 2013. 46 p.
Series
Umeå University medical dissertations, ISSN 0346-6612 ; 1596
Keyword
Lens, retina, BMP, FGF, chick
National Category
Developmental Biology
Research subject
Developmental Biology
Identifiers
urn:nbn:se:umu:diva-80192 (URN)978-91-7459-725-7 (ISBN)
Public defence
2013-10-04, Hörsal B, Unod T 9, Norrlands Universitetssjukhus(NUS), Umeå, 13:00 (English)
Opponent
Supervisors
Available from: 2013-09-13 Created: 2013-09-11 Last updated: 2013-09-13Bibliographically approved
2. BMP - a key signaling molecule in specification and morphogenesis of sensory structures
Open this publication in new window or tab >>BMP - a key signaling molecule in specification and morphogenesis of sensory structures
2016 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Cranial placodes are transient thickenings of the vertebrate embryonic head ectoderm that will give rise to sensory (olfactory, lens, and otic) and non-sensory (hypophyseal) components of the peripheral nervous system (PNS). In most vertebrate embryos, these four sensory placodes undergo invagination. Epithelial invagination is a morphological process in which flat cell sheets transform into three-dimensional structures, like an epithelial pit/cup. The process of invagination is crucial during development as it plays an important role for the formation of the lens, inner ear, nasal cavity, and adenohypophysis. Using the chick as the model system the following questions were addressed. What signals are involved in placode invagination? Is there any common regulatory molecular mechanism for all sensory placode invagination, or is it controlled by unique molecular codes for each individual placode? Are placode invagination and acquisition of placode-specific identities two independent developmental processes or coupled together? To address this we used in vivo assays like electroporation and whole embryo culture. Our in vivo results provide evidence that RhoA and F-actin rearrangements, apical constriction, cell elongation and epithelial invagination are regulated by a common BMP (Bone morphogenetic protein) dependent molecular mechanism. In addition, our results show that epithelial invagination and acquisition of placode-specific identities are two independent developmental processes.

BMP signals have been shown to be essential for lens development and patterning of the retina. However, the spatial and temporal requirement of BMP activity during early events of lens development has remained elusive. Moreover, when and how retinal cells are specified, and whether the lens plays any role for the early development of the retina is not completely known. To address these questions, we have used gain- and loss-of-function analyses in chick explant and intact embryo assays. Here, we show that during lens development BMP activity is both required and sufficient to induce the lens specific marker, L-Maf. After the L-Maf upregulation the cells are no longer dependent on BMP signaling for the next step of fiber cell differentiation, which is characterized by up-regulation of δ-crystallin expression. Regarding the specification of retinal cells our results provide evidence that at blastula stages, BMP signals inhibit the acquisition of eye-field character. Furthermore, from optic vesicle stages, BMP signals emanating from the lens are essential for maintaining eye-field identity, inhibiting telencephalic character and inducing neural retina cells.

Place, publisher, year, edition, pages
Umeå: Umeå University, 2016. 64 p.
Series
Umeå University medical dissertations, ISSN 0346-6612 ; 1812
Keyword
BMP signaling, Placode morphogenesis, lens, retina, olfactory, otic
National Category
Developmental Biology
Research subject
Developmental Biology
Identifiers
urn:nbn:se:umu:diva-119696 (URN)978-91-7601-468-4 (ISBN)
Public defence
2016-05-20, Hörsal B Unod T 9, Norrlands universitetssjukhus, Umeå, 09:00 (English)
Opponent
Supervisors
Available from: 2016-04-29 Created: 2016-04-25 Last updated: 2016-04-28Bibliographically approved

Open Access in DiVA

No full text

Other links

Publisher's full textPubMed

Search in DiVA

By author/editor
Pandit, TanushreeJidigam, Vijay KGunhaga, Lena
By organisation
Umeå Centre for Molecular Medicine (UCMM)
In the same journal
Developmental Dynamics
Developmental BiologyCell and Molecular Biology

Search outside of DiVA

GoogleGoogle Scholar

doi
pubmed
urn-nbn

Altmetric score

doi
pubmed
urn-nbn
Total: 180 hits
CiteExportLink to record
Permanent link

Direct link
Cite
Citation style
  • apa
  • ieee
  • modern-language-association-8th-edition
  • vancouver
  • Other style
More styles
Language
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Other locale
More languages
Output format
  • html
  • text
  • asciidoc
  • rtf