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Ivanovitch, K.

Publications and source records attributed to Ivanovitch, K..

3 recordsLinked to original sources

A method for analysing tissue motion and deformation during mammalian organogenesis

Understanding tissue morphogenesis is an important goal in developmental biology and tissue engineering. Accurately describing tissue deformation processes and how cell rearrangements contribute to these is a challenging task. Live analysis of morphogenesis in 3D is frequently used to obtain source data that allow to extract such features from developing organs. However, several limitations are encountered when applying these methodologies to mammalian embryos. The mouse embryo is the most frequently used model, but most studies use a very limited number of specimens and present only individual acquisitions due to constraints imposed by embryo culture and imaging. Here we used data from live analysis of embryonic heart development to develop methodologies that allow to 1) deduce tissue deformation and cell movements from image intensity flows, 2) stage and register data from several specimens/acquisitions to a dynamic consensus model of heart development, 3) statistically calculate and map to the model tissue growth and anisotropy and 4) generate a digital model of heart development that allows in-silico pseudo-cell fate mapping. Our methodology will greatly facilitate the understanding of morphogenetic processes underlying mammalian organogenesis.

developmental biology↗

Developmental cell fate choice employs two distinct cis regulatory strategies

In many developing tissues the patterns of gene expression that assign cell fate are organised by secreted signals functioning in a graded manner over multiple cell diameters. Cis Regulatory Elements (CREs) interpret these graded inputs to control gene expression. How this is accomplished remains poorly understood. In the neural tube, a gradient of the morphogen Sonic hedgehog allocates neural progenitor identity. Here, we uncover two distinct ways in which CREs translate graded Shh signaling into differential gene expression. In the majority of ventral neural progenitors a common set of CREs are used to control gene activity. These CREs integrate cell type specific inputs to control gene expression. By contrast, the most ventral progenitors use a unique set of CREs. These are established by the pioneer factor FOXA2, paralleling the role of FOXA2 in endoderm. Moreover, FOXA2 binds a subset of the same sites in neural and endoderm cells. Together the data identify distinct cis regulatory strategies for the interpretation of morphogen signaling and raise the possibility of an evolutionarily conserved role for FOXA2-mediated regulatory strategy across tissues.

developmental biology↗

Live imaging of heart tube development in mouse reveals alternating phases of cardiac differentiation and morphogenesis

During vertebrate heart development two progenitor populations, first and second heart fields (FHF, SHF), sequentially contribute to longitudinal subdivisions of the heart tube (HT), with the FHF contributing the left ventricle and part of the atria, and the SHF the rest of the heart. Here we study the dynamics of cardiac differentiation and morphogenesis by tracking individual cells in live analysis of mouse embryos. We report that during an initial phase, FHF precursors differentiate rapidly to form a cardiac crescent, while limited morphogenesis takes place. In a second phase, no differentiation occurs while extensive morphogenesis, including splanchnic mesoderm sliding over the endoderm, results in HT formation. In a third phase, cardiac precursor differentiation resumes and contributes to SHF-derived regions and the dorsal closure of the HT. These results reveal tissue-level coordination between morphogenesis and differentiation during HT formation and provide a new framework to understand heart development.

developmental biology↗