Coordination of Cell Fate Specification and Cell Movements by Morphogenetic Gradients
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ndltd-OhioLink-oai-etd.ohiolink.edu-case16080305650006552021-08-03T07:16:40Z Coordination of Cell Fate Specification and Cell Movements by Morphogenetic Gradients Xue, Yongqiang Biology Developmental Biology Molecular Biology Morphogenetic gradient positional information cell movment Decapentaplegic Dorsal Frazzled GUK-holder Morphogens are chemical substances that establish gradients of concentration across developmental fields and regulate cell fate specification by activating or repressing target genes in a dosage-dependent manner. In most developmental fields, cells are constantly being displaced in space at the same time they receive positional information from morphogens, yet their fates are correctly specified. In this dissertation, we investigated how morphogens coordinate cell fate specification and cell movements in dynamic developmental fields. To address our question, we focused on the dorsoventral patterning of Drosophila melanogaster blastoderm embryos, where the mesodermal, neuroectodermal and ectodermal germ layers are formed. Two opposing morphogen gradients establish these fates: the ventral-to-dorsal maternal Dorsal (DL)/NF-κB nuclear concentration gradient and the dorsal-to-ventral Decapentaplegic (DPP)/Bone Morphogenetic Protein-4 (BMP-4) gradient. Although the cellularization stage has long been considered static and it was assumed that cells perceived the local morphogen concentrations without changing their positions, cells at that stage actually follow a stereotyped migration trajectory consisting of moving from the embryo lateral sides and the poles towards the dorsal midline. Our results show that DPP attracts cells to its region of peak activity levels in the dorsal midline, while DL counteracts DPP attraction by maintaining cells mostly immobile in the ventral region. We identified two genes, frazzled (fra) and GUK-holder (gukh), that function as downstream effectors of DL and DPP, which are necessary for the stereotyped cell migrations. Finally, we showed that fra and gukh are required for the correct DV gene patterning by modifying the DL and DPP gradient thresholds. We propose that morphogens coordinate cell fate specification not only by the well-studied dosage-dependent manner but also by orchestrating morphogenetic cell movements that ultimately leads to an adjustment of gradient shapes that is required for correct patterning. 2021-01-22 English text Case Western Reserve University School of Graduate Studies / OhioLINK http://rave.ohiolink.edu/etdc/view?acc_num=case1608030565000655 http://rave.ohiolink.edu/etdc/view?acc_num=case1608030565000655 restricted--full text unavailable until 2023-01-15 This thesis or dissertation is protected by copyright: some rights reserved. It is licensed for use under a Creative Commons license. Specific terms and permissions are available from this document's record in the OhioLINK ETD Center. |
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language |
English |
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topic |
Biology Developmental Biology Molecular Biology Morphogenetic gradient positional information cell movment Decapentaplegic Dorsal Frazzled GUK-holder |
spellingShingle |
Biology Developmental Biology Molecular Biology Morphogenetic gradient positional information cell movment Decapentaplegic Dorsal Frazzled GUK-holder Xue, Yongqiang Coordination of Cell Fate Specification and Cell Movements by Morphogenetic Gradients |
author |
Xue, Yongqiang |
author_facet |
Xue, Yongqiang |
author_sort |
Xue, Yongqiang |
title |
Coordination of Cell Fate Specification and Cell Movements by Morphogenetic Gradients |
title_short |
Coordination of Cell Fate Specification and Cell Movements by Morphogenetic Gradients |
title_full |
Coordination of Cell Fate Specification and Cell Movements by Morphogenetic Gradients |
title_fullStr |
Coordination of Cell Fate Specification and Cell Movements by Morphogenetic Gradients |
title_full_unstemmed |
Coordination of Cell Fate Specification and Cell Movements by Morphogenetic Gradients |
title_sort |
coordination of cell fate specification and cell movements by morphogenetic gradients |
publisher |
Case Western Reserve University School of Graduate Studies / OhioLINK |
publishDate |
2021 |
url |
http://rave.ohiolink.edu/etdc/view?acc_num=case1608030565000655 |
work_keys_str_mv |
AT xueyongqiang coordinationofcellfatespecificationandcellmovementsbymorphogeneticgradients |
_version_ |
1719457912512839680 |