Cell and Developmental Biology (Schier)Head of Research Unit Prof. Dr. Alexander Schier, Prof. Dr.OverviewMembersPublicationsProjects & CollaborationsProjects & Collaborations OverviewMembersPublicationsProjects & Collaborations Projects & Collaborations 21 foundShow per page10 10 20 50 SELFORGANIZE / Mechanisms of self-organized axis formation in vivo Research Project | 2 Project MembersImported from Grants Tool 4707034 Enhancing transplant viability by using condensate modulators inspired by nature Research Project | 1 Project MembersImported from Grants Tool 4718162 Morphogen signaling and mechanotransduction in early killifish embryogenesis Research Project | 2 Project MembersImported from Grants Tool 4709749 MECHANISMS OF BODY-BRAIN COMMUNICATION IN ORGAN FUNCTION AND BEHAVIOR Research Project | 1 Project MembersImported from Grants Tool 4705266 The cis regulatory code of translational control during embryogenesis Research Project | 1 Project MembersImported from Grants Tool 4701316 The cis-regulatory code of Nodal morphogen interpretation Research Project | 1 Project MembersImported from Grants Tool 4701080 The functional and molecular evolution of thermosensation in nematode worms Research Project | 1 Project MembersImported from Grants Tool 4665048 DevBoundaries - Formation of tissue boundaries during zebrafish embryogenesis Research Project | 2 Project MembersDuring animal development, boundaries need to be established between cell types to guarantee the physical and functional integrity of tissues. However, the underlying mechanisms are poorly understood because it has been challenging to analyze the coordination of gene expression, cell proliferation and cell movement needed for boundary formation. I will probe the in vivo mechanisms of boundary formation using the zebrafish embryonic shield region as a model system. The shield contains overlapping progenitor cells that give rise to various midline structures whose boundaries form and sharpen during gastrulation. I will use imaging and genetic approaches to determine how shield cells differentiate and generate tissue boundaries. Aim 1: To characterize lineage, movement and differentiation of shield progenitors and their descendants, I will use in toto light-sheet imaging. This approach will generate a dynamic atlas detailing the cellular basis of boundary formation. Aim 2: To characterize the gene expression changes during the separation of shield progenitors and their descendants, I will use spatial transcriptomics. This aim will create a dynamic atlas detailing the transcriptomic basis of boundary formation. Aim 3: To define the molecular basis of boundary formation, I will disrupt candidate genes involved in boundary formation. This approach will determine if differentiation and morphogenesis are coupled during boundary formation and define molecular pathways that ensure robust boundary formation. Together, the proposed approaches will identify cellular and genetic mechanisms controlling boundary formation during embryogenesis. Allen Discovery Center for Cell Lineage Renewal Research Project | 2 Project MembersMulticellular organisms develop by way of a lineage tree, a series of cell divisions and molecular changes that give rise to cell types, tissues and organs. Despite their fundamental relevance to development, our knowledge of cell lineages and their determinants remains fragmentary, and fundamental questions remain unanswered: What are the molecular and cellular programs that drive cells to acquire specific fates? How do these vary within an individual, between individuals, and across species? What are the cell lineage motifs that underlie consistencies and differences in form and function? In its first phase, our Center has established novel paradigms for recording cell lineage and cell states. We can introduce heritable and cumulative changes into the genome to record the lineage relationship between cells (scGESTALT; MEMOIR). We can measure the transcriptional and epigenetic states of cells and reconstruct the molecular trajectories underlying cell type differentiation (sci-seq). We can measure transcriptomes and lineage markers in tissues and reconstruct the spatiotemporal unfolding of development (seqFISH; sci-Space). In C. elegans , we have used such information to define developmental principles such as multilineage priming. In C. elegans , Drosophila , zebrafish and mouse, we have used our datasets to define cellular diversity and regulators of cell type differentiation. We now have the methodological foundation to address fundamental questions in developmental biology at the scale of the entire vertebrate embryo. In order to reveal developmental rules that are shared and divergent across individuals and species, we propose to map (Aim 1), model (Aim 2) and manipulate (Aim 3) embryogenesis. We will focus on zebrafish and mouse embryogenesis, because these are well-established and accessible model systems in which we have laid the requisite groundwork. In Aim 1 , we will use genomic and imaging approaches to generate high-resolution maps of natural zebrafish and mouse embryogenesis and of stem cell-derived synthetic mouse embryogenesis. Maps will include cell lineage, gene expression, chromatin accessibility data and signaling activity and will be complemented by live imaging of cell movements. In Aim 2 , we will integrate these datasets to generate a consensus scaffold of the molecular trajectories and lineage structures of embryogenesis, together with statistical models that seek to explain developmental processes in terms of rates of cell division and probabilistic differentiation. In a complementary approach, we will develop lineage motif analysis, a framework for extracting the key recurrent programs of cell lineage histories in relation to time, space and molecular state. We will then apply both the consensus model and lineage motif analysis to investigate different kinds of developmental variation: interclonal, interindividual and interspecies. We will make our tools, datasets, models and insights available to the community through a navigable 'virtual embryo'. In Aim 3 , we will functionally test model predictions and address how genetic, embryological or environmental manipulations affect cell fate decisions, lineage variation and developmental robustness. We will manipulate key parameters of development such as the activity of lineage regulators and intercellular interactions, cell number and proliferation rates in different lineages, and environmental and metabolic conditions. The observed phenotypic consequences will shed light on the mechanisms underlying developmental robustness and variation. DevUTRs - Uncovering the roles of 5′UTRs in translational control during early zebrafish development (Marie Curie Fellowship Madalena Pinto) Research Project | 2 Project MembersDuring early developmental stages, metazoan embryos are transcriptionally silent, and embryogenesis is controlled by maternally deposited factors. Developmental progression requires the synthesis of new mRNAs and proteins in a coordinated fashion. Many posttranscriptional mechanisms regulate the fate of maternal mRNAs, but it is less understood how translational control shapes early embryogenesis. Protein synthesis is primarily regulated at the translation initiation step by elements in the 5′ untranslated region (5′ UTR) of the mRNA. However, we currently lack a systematic understanding of the regulatory information contained within 5′ UTRs and how they functionally impact mRNA translation throughout development. Using zebrafish as a model of vertebrate development, we are developing an in vivo massively parallel reporter assay (MPRA) to identify 5′ UTR motifs involved in translation regulation. By integrating the translational behaviour of 5′ UTR reporters throughout embryogenesis with sequence-based regression models, we anticipate to uncover novel cis -regulatory elements in 5′ UTRs with developmental roles. The MPRA will lay the foundation for future studies dissecting the molecular mechanisms underlying the function of newly identified 5′ UTR motifs. 123 123 OverviewMembersPublicationsProjects & Collaborations
Projects & Collaborations 21 foundShow per page10 10 20 50 SELFORGANIZE / Mechanisms of self-organized axis formation in vivo Research Project | 2 Project MembersImported from Grants Tool 4707034 Enhancing transplant viability by using condensate modulators inspired by nature Research Project | 1 Project MembersImported from Grants Tool 4718162 Morphogen signaling and mechanotransduction in early killifish embryogenesis Research Project | 2 Project MembersImported from Grants Tool 4709749 MECHANISMS OF BODY-BRAIN COMMUNICATION IN ORGAN FUNCTION AND BEHAVIOR Research Project | 1 Project MembersImported from Grants Tool 4705266 The cis regulatory code of translational control during embryogenesis Research Project | 1 Project MembersImported from Grants Tool 4701316 The cis-regulatory code of Nodal morphogen interpretation Research Project | 1 Project MembersImported from Grants Tool 4701080 The functional and molecular evolution of thermosensation in nematode worms Research Project | 1 Project MembersImported from Grants Tool 4665048 DevBoundaries - Formation of tissue boundaries during zebrafish embryogenesis Research Project | 2 Project MembersDuring animal development, boundaries need to be established between cell types to guarantee the physical and functional integrity of tissues. However, the underlying mechanisms are poorly understood because it has been challenging to analyze the coordination of gene expression, cell proliferation and cell movement needed for boundary formation. I will probe the in vivo mechanisms of boundary formation using the zebrafish embryonic shield region as a model system. The shield contains overlapping progenitor cells that give rise to various midline structures whose boundaries form and sharpen during gastrulation. I will use imaging and genetic approaches to determine how shield cells differentiate and generate tissue boundaries. Aim 1: To characterize lineage, movement and differentiation of shield progenitors and their descendants, I will use in toto light-sheet imaging. This approach will generate a dynamic atlas detailing the cellular basis of boundary formation. Aim 2: To characterize the gene expression changes during the separation of shield progenitors and their descendants, I will use spatial transcriptomics. This aim will create a dynamic atlas detailing the transcriptomic basis of boundary formation. Aim 3: To define the molecular basis of boundary formation, I will disrupt candidate genes involved in boundary formation. This approach will determine if differentiation and morphogenesis are coupled during boundary formation and define molecular pathways that ensure robust boundary formation. Together, the proposed approaches will identify cellular and genetic mechanisms controlling boundary formation during embryogenesis. Allen Discovery Center for Cell Lineage Renewal Research Project | 2 Project MembersMulticellular organisms develop by way of a lineage tree, a series of cell divisions and molecular changes that give rise to cell types, tissues and organs. Despite their fundamental relevance to development, our knowledge of cell lineages and their determinants remains fragmentary, and fundamental questions remain unanswered: What are the molecular and cellular programs that drive cells to acquire specific fates? How do these vary within an individual, between individuals, and across species? What are the cell lineage motifs that underlie consistencies and differences in form and function? In its first phase, our Center has established novel paradigms for recording cell lineage and cell states. We can introduce heritable and cumulative changes into the genome to record the lineage relationship between cells (scGESTALT; MEMOIR). We can measure the transcriptional and epigenetic states of cells and reconstruct the molecular trajectories underlying cell type differentiation (sci-seq). We can measure transcriptomes and lineage markers in tissues and reconstruct the spatiotemporal unfolding of development (seqFISH; sci-Space). In C. elegans , we have used such information to define developmental principles such as multilineage priming. In C. elegans , Drosophila , zebrafish and mouse, we have used our datasets to define cellular diversity and regulators of cell type differentiation. We now have the methodological foundation to address fundamental questions in developmental biology at the scale of the entire vertebrate embryo. In order to reveal developmental rules that are shared and divergent across individuals and species, we propose to map (Aim 1), model (Aim 2) and manipulate (Aim 3) embryogenesis. We will focus on zebrafish and mouse embryogenesis, because these are well-established and accessible model systems in which we have laid the requisite groundwork. In Aim 1 , we will use genomic and imaging approaches to generate high-resolution maps of natural zebrafish and mouse embryogenesis and of stem cell-derived synthetic mouse embryogenesis. Maps will include cell lineage, gene expression, chromatin accessibility data and signaling activity and will be complemented by live imaging of cell movements. In Aim 2 , we will integrate these datasets to generate a consensus scaffold of the molecular trajectories and lineage structures of embryogenesis, together with statistical models that seek to explain developmental processes in terms of rates of cell division and probabilistic differentiation. In a complementary approach, we will develop lineage motif analysis, a framework for extracting the key recurrent programs of cell lineage histories in relation to time, space and molecular state. We will then apply both the consensus model and lineage motif analysis to investigate different kinds of developmental variation: interclonal, interindividual and interspecies. We will make our tools, datasets, models and insights available to the community through a navigable 'virtual embryo'. In Aim 3 , we will functionally test model predictions and address how genetic, embryological or environmental manipulations affect cell fate decisions, lineage variation and developmental robustness. We will manipulate key parameters of development such as the activity of lineage regulators and intercellular interactions, cell number and proliferation rates in different lineages, and environmental and metabolic conditions. The observed phenotypic consequences will shed light on the mechanisms underlying developmental robustness and variation. DevUTRs - Uncovering the roles of 5′UTRs in translational control during early zebrafish development (Marie Curie Fellowship Madalena Pinto) Research Project | 2 Project MembersDuring early developmental stages, metazoan embryos are transcriptionally silent, and embryogenesis is controlled by maternally deposited factors. Developmental progression requires the synthesis of new mRNAs and proteins in a coordinated fashion. Many posttranscriptional mechanisms regulate the fate of maternal mRNAs, but it is less understood how translational control shapes early embryogenesis. Protein synthesis is primarily regulated at the translation initiation step by elements in the 5′ untranslated region (5′ UTR) of the mRNA. However, we currently lack a systematic understanding of the regulatory information contained within 5′ UTRs and how they functionally impact mRNA translation throughout development. Using zebrafish as a model of vertebrate development, we are developing an in vivo massively parallel reporter assay (MPRA) to identify 5′ UTR motifs involved in translation regulation. By integrating the translational behaviour of 5′ UTR reporters throughout embryogenesis with sequence-based regression models, we anticipate to uncover novel cis -regulatory elements in 5′ UTRs with developmental roles. The MPRA will lay the foundation for future studies dissecting the molecular mechanisms underlying the function of newly identified 5′ UTR motifs. 123 123
SELFORGANIZE / Mechanisms of self-organized axis formation in vivo Research Project | 2 Project MembersImported from Grants Tool 4707034
Enhancing transplant viability by using condensate modulators inspired by nature Research Project | 1 Project MembersImported from Grants Tool 4718162
Morphogen signaling and mechanotransduction in early killifish embryogenesis Research Project | 2 Project MembersImported from Grants Tool 4709749
MECHANISMS OF BODY-BRAIN COMMUNICATION IN ORGAN FUNCTION AND BEHAVIOR Research Project | 1 Project MembersImported from Grants Tool 4705266
The cis regulatory code of translational control during embryogenesis Research Project | 1 Project MembersImported from Grants Tool 4701316
The cis-regulatory code of Nodal morphogen interpretation Research Project | 1 Project MembersImported from Grants Tool 4701080
The functional and molecular evolution of thermosensation in nematode worms Research Project | 1 Project MembersImported from Grants Tool 4665048
DevBoundaries - Formation of tissue boundaries during zebrafish embryogenesis Research Project | 2 Project MembersDuring animal development, boundaries need to be established between cell types to guarantee the physical and functional integrity of tissues. However, the underlying mechanisms are poorly understood because it has been challenging to analyze the coordination of gene expression, cell proliferation and cell movement needed for boundary formation. I will probe the in vivo mechanisms of boundary formation using the zebrafish embryonic shield region as a model system. The shield contains overlapping progenitor cells that give rise to various midline structures whose boundaries form and sharpen during gastrulation. I will use imaging and genetic approaches to determine how shield cells differentiate and generate tissue boundaries. Aim 1: To characterize lineage, movement and differentiation of shield progenitors and their descendants, I will use in toto light-sheet imaging. This approach will generate a dynamic atlas detailing the cellular basis of boundary formation. Aim 2: To characterize the gene expression changes during the separation of shield progenitors and their descendants, I will use spatial transcriptomics. This aim will create a dynamic atlas detailing the transcriptomic basis of boundary formation. Aim 3: To define the molecular basis of boundary formation, I will disrupt candidate genes involved in boundary formation. This approach will determine if differentiation and morphogenesis are coupled during boundary formation and define molecular pathways that ensure robust boundary formation. Together, the proposed approaches will identify cellular and genetic mechanisms controlling boundary formation during embryogenesis.
Allen Discovery Center for Cell Lineage Renewal Research Project | 2 Project MembersMulticellular organisms develop by way of a lineage tree, a series of cell divisions and molecular changes that give rise to cell types, tissues and organs. Despite their fundamental relevance to development, our knowledge of cell lineages and their determinants remains fragmentary, and fundamental questions remain unanswered: What are the molecular and cellular programs that drive cells to acquire specific fates? How do these vary within an individual, between individuals, and across species? What are the cell lineage motifs that underlie consistencies and differences in form and function? In its first phase, our Center has established novel paradigms for recording cell lineage and cell states. We can introduce heritable and cumulative changes into the genome to record the lineage relationship between cells (scGESTALT; MEMOIR). We can measure the transcriptional and epigenetic states of cells and reconstruct the molecular trajectories underlying cell type differentiation (sci-seq). We can measure transcriptomes and lineage markers in tissues and reconstruct the spatiotemporal unfolding of development (seqFISH; sci-Space). In C. elegans , we have used such information to define developmental principles such as multilineage priming. In C. elegans , Drosophila , zebrafish and mouse, we have used our datasets to define cellular diversity and regulators of cell type differentiation. We now have the methodological foundation to address fundamental questions in developmental biology at the scale of the entire vertebrate embryo. In order to reveal developmental rules that are shared and divergent across individuals and species, we propose to map (Aim 1), model (Aim 2) and manipulate (Aim 3) embryogenesis. We will focus on zebrafish and mouse embryogenesis, because these are well-established and accessible model systems in which we have laid the requisite groundwork. In Aim 1 , we will use genomic and imaging approaches to generate high-resolution maps of natural zebrafish and mouse embryogenesis and of stem cell-derived synthetic mouse embryogenesis. Maps will include cell lineage, gene expression, chromatin accessibility data and signaling activity and will be complemented by live imaging of cell movements. In Aim 2 , we will integrate these datasets to generate a consensus scaffold of the molecular trajectories and lineage structures of embryogenesis, together with statistical models that seek to explain developmental processes in terms of rates of cell division and probabilistic differentiation. In a complementary approach, we will develop lineage motif analysis, a framework for extracting the key recurrent programs of cell lineage histories in relation to time, space and molecular state. We will then apply both the consensus model and lineage motif analysis to investigate different kinds of developmental variation: interclonal, interindividual and interspecies. We will make our tools, datasets, models and insights available to the community through a navigable 'virtual embryo'. In Aim 3 , we will functionally test model predictions and address how genetic, embryological or environmental manipulations affect cell fate decisions, lineage variation and developmental robustness. We will manipulate key parameters of development such as the activity of lineage regulators and intercellular interactions, cell number and proliferation rates in different lineages, and environmental and metabolic conditions. The observed phenotypic consequences will shed light on the mechanisms underlying developmental robustness and variation.
DevUTRs - Uncovering the roles of 5′UTRs in translational control during early zebrafish development (Marie Curie Fellowship Madalena Pinto) Research Project | 2 Project MembersDuring early developmental stages, metazoan embryos are transcriptionally silent, and embryogenesis is controlled by maternally deposited factors. Developmental progression requires the synthesis of new mRNAs and proteins in a coordinated fashion. Many posttranscriptional mechanisms regulate the fate of maternal mRNAs, but it is less understood how translational control shapes early embryogenesis. Protein synthesis is primarily regulated at the translation initiation step by elements in the 5′ untranslated region (5′ UTR) of the mRNA. However, we currently lack a systematic understanding of the regulatory information contained within 5′ UTRs and how they functionally impact mRNA translation throughout development. Using zebrafish as a model of vertebrate development, we are developing an in vivo massively parallel reporter assay (MPRA) to identify 5′ UTR motifs involved in translation regulation. By integrating the translational behaviour of 5′ UTR reporters throughout embryogenesis with sequence-based regression models, we anticipate to uncover novel cis -regulatory elements in 5′ UTRs with developmental roles. The MPRA will lay the foundation for future studies dissecting the molecular mechanisms underlying the function of newly identified 5′ UTR motifs.
