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  • 1.
    Jidigam, Vijay
    et al.
    Umeå University, Faculty of Medicine, Umeå Centre for Molecular Medicine (UCMM).
    Gunhaga, Lena
    Umeå University, Faculty of Medicine, Umeå Centre for Molecular Medicine (UCMM).
    Role of BMP signaling on cytoskeleton elements in the sensory placode invagination2014In: Molecular Biology of the Cell, ISSN 1059-1524, E-ISSN 1939-4586, Vol. 25, article id P1653Article in journal (Other academic)
  • 2.
    Jidigam, Vijay K.
    et al.
    Umeå University, Faculty of Medicine, Umeå Centre for Molecular Medicine (UCMM).
    Gunhaga, Lena
    Umeå University, Faculty of Medicine, Umeå Centre for Molecular Medicine (UCMM).
    Development of cranial placodes: insights from studies in chick2013In: Development, Growth and Differentiation, ISSN 0012-1592, E-ISSN 1440-169X, Vol. 55, no 1, p. 79-95Article, review/survey (Refereed)
    Abstract [en]

    This review focuses on how research, using chick as a model system, has contributed to our knowledge regarding the development of cranial placodes. This review highlights when and how molecular signaling events regulate early specification of placodal progenitor cells, as well as the development of individual placodes including morphological movements. In addition, we briefly describe various techniques used in chick that are important for studies in cell and developmental biology.

  • 3.
    Jidigam, Vijay K.
    et al.
    Umeå University, Faculty of Medicine, Umeå Centre for Molecular Medicine (UCMM).
    Srinivasan, Raghuraman C.
    Umeå University, Faculty of Medicine, Umeå Centre for Molecular Medicine (UCMM).
    Patthey, Cedric
    Umeå University, Faculty of Medicine, Umeå Centre for Molecular Medicine (UCMM).
    Gunhaga, Lena
    Umeå University, Faculty of Medicine, Umeå Centre for Molecular Medicine (UCMM).
    Apical constriction and epithelial invagination are regulated by BMP activity2015In: Biology open, ISSN 2046-6390, Vol. 4, no 12, p. 1782-1791Article in journal (Refereed)
    Abstract [en]

    Epithelial invagination is a morphological process in which flat cell sheets transform into three-dimensional structures through bending of the tissue. It is accompanied by apical constriction, in which the apical cell surface is reduced in relation to the basal cell surface. Although much is known about the intra-cellular molecular machinery driving apical constriction and epithelial invagination, information of how extra-cellular signals affect these processes remains insufficient. In this study we have established several in vivo assays of placodal invagination to explore whether the external signal BMP regulates processes connected to epithelial invagination. By inhibiting BMP activity in prospective cranial placodes, we provide evidence that BMP signals are required for RhoA and F-actin rearrangements, apical constriction, cell elongation and epithelial invagination. The failure of placode invagination after BMP inhibition appears to be a direct consequence of disrupted apical accumulation of RhoA and F-actin, rather than changes in cell death or proliferation. In addition, our results show that epithelial invagination and acquisition of placode-specific identities are two distinct and separable developmental processes. In summary, our results provide evidence that BMP signals promote epithelial invagination by acting upstream of the intracellular molecular machinery that drives apical constriction and cell elongation.

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  • 4.
    Jidigam, Vijay Kumar
    Umeå University, Faculty of Medicine, Umeå Centre for Molecular Medicine (UCMM).
    BMP - a key signaling molecule in specification and morphogenesis of sensory structures2016Doctoral 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.

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  • 5.
    Panaliappan, Tamilarasan K.
    et al.
    Umeå University, Faculty of Medicine, Umeå Centre for Molecular Medicine (UCMM).
    Wittmann, Walter
    Umeå University, Faculty of Medicine, Umeå Centre for Molecular Medicine (UCMM).
    Jidigam, Vijay K.
    Umeå University, Faculty of Medicine, Umeå Centre for Molecular Medicine (UCMM).
    Mercurio, Sara
    Bertolini, Jessica A.
    Sghari, Soufien
    Umeå University, Faculty of Medicine, Umeå Centre for Molecular Medicine (UCMM).
    Bose, Raj
    Umeå University, Faculty of Medicine, Umeå Centre for Molecular Medicine (UCMM).
    Patthey, Cedric
    Umeå University, Faculty of Medicine, Umeå Centre for Molecular Medicine (UCMM).
    Nicolis, Silvia K.
    Gunhaga, Lena
    Umeå University, Faculty of Medicine, Umeå Centre for Molecular Medicine (UCMM).
    Sox2 is required for olfactory pit formation and olfactory neurogenesis through BMP restriction and Hes5 upregulation2018In: Development, ISSN 0950-1991, E-ISSN 1477-9129, Vol. 145, no 2, article id dev153791Article in journal (Refereed)
    Abstract [en]

    The transcription factor Sox2 is necessary to maintain pluripotency of embryonic stem cells, and to regulate neural development. Neurogenesis in the vertebrate olfactory epithelium persists from embryonic stages through adulthood. The role Sox2 plays for the development of the olfactory epithelium and neurogenesis within has, however, not been determined. Here, by analysing Sox2 conditional knockout mouse embryos and chick embryos deprived of Sox2 in the olfactory epithelium using CRISPR-Cas9, we show that Sox2 activity is crucial for the induction of the neural progenitor gene Hes5 and for subsequent differentiation of the neuronal lineage. Our results also suggest that Sox2 activity promotes the neurogenic domain in the nasal epithelium by restricting Bmp4 expression. The Sox2-deficient olfactory epithelium displays diminished cell cycle progression and proliferation, a dramatic increase in apoptosis and finally olfactory pit atrophy. Moreover, chromatin immunoprecipitation data show that Sox2 directly binds to the Hes5 promoter in both the PNS and CNS. Taken together, our results indicate that Sox2 is essential to establish, maintain and expand the neuronal progenitor pool by suppressing Bmp4 and upregulating Hes5 expression.

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  • 6.
    Pandit, Tanushree
    et al.
    Umeå University, Faculty of Medicine, Umeå Centre for Molecular Medicine (UCMM).
    Jidigam, Vijay K
    Umeå University, Faculty of Medicine, Umeå Centre for Molecular Medicine (UCMM).
    Gunhaga, Lena
    Umeå University, Faculty of Medicine, Umeå Centre for Molecular Medicine (UCMM).
    BMP-induced L-Maf regulates subsequent BMP-independent differentiation of primary lens fibre cells2011In: Developmental Dynamics, ISSN 1058-8388, E-ISSN 1097-0177, Vol. 240, no 8, p. 1917-1928Article in journal (Refereed)
    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.

  • 7.
    Pandit, Tanushree
    et al.
    Umeå University, Faculty of Medicine, Umeå Centre for Molecular Medicine (UCMM).
    Jidigam, Vijay Kumar
    Umeå University, Faculty of Medicine, Umeå Centre for Molecular Medicine (UCMM).
    Patthey, Cedric
    Umeå University, Faculty of Medicine, Umeå Centre for Molecular Medicine (UCMM).
    Gunhaga, Lena
    Umeå University, Faculty of Medicine, Umeå Centre for Molecular Medicine (UCMM).
    Neural retina identity is specified by lens-derived BMP signals2015In: Development, ISSN 0950-1991, E-ISSN 1477-9129, Vol. 142, no 10, p. 1850-1859Article in journal (Refereed)
    Abstract [en]

    The eye has served as a classical model to study cell specification and tissue induction for over a century. Nevertheless, the molecular mechanisms that regulate the induction and maintenance of eye-field cells, and the specification of neural retina cells are poorly understood. Moreover, within the developing anterior forebrain, how prospective eye and telencephalic cells are differentially specified is not well defined. In the present study, we have analyzed these issues by manipulating signaling pathways in intact chick embryo and explant assays. Our results provide evidence that at blastula stages, BMP signals inhibit the acquisition of eye-field character, but from neural tube/optic vesicle stages, BMP signals from the lens are crucial for the maintenance of eye-field character, inhibition of dorsal telencephalic cell identity and specification of neural retina cells. Subsequently, our results provide evidence that a Rax2-positive eye-field state is not sufficient for the progress to a neural retina identity, but requires BMP signals. In addition, our results argue against any essential role of Wnt or FGF signals during the specification of neural retina cells, but provide evidence that Wnt signals together with BMP activity are sufficient to induce cells of retinal pigment epithelial character. We conclude that BMP activity emanating from the lens ectoderm maintains eye-field identity, inhibits telencephalic character and induces neural retina cells. Our findings link the requirement of the lens ectoderm for neural retina specification with the molecular mechanism by which cells in the forebrain become specified as neural retina by BMP activity.

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