Morphogenesis: Biophysics and Genetics of Dorsal Closure
Morphogenesis: Biophysics and Genetics of Dorsal Closure
批准号:
10623612
负责人:
DANIEL PETER KIEHART
金额:
$51.74万
依托单位:
依托单位国家:
美国
项目类别:
财政年份:
2018
资助国家:
美国
项目状态:
未结题
起止时间:
2018-07-01 至 2028-06-30
关键词:
ActomyosinAddressAdhesionsAnimalsBiochemicalBiologicalBiological ModelsBiological ProcessBiophysical ProcessBiophysicsCell CommunicationCell ShapeCellsCellular biologyCharacteristicsChromosomesCleft PalateComplexCytoskeletonDefectDevelopmentDevelopmental ProcessDorsalDrosophila genusDrosophila melanogasterEmbryoEpitheliumFunctional disorderGene ExpressionGenesGeneticGenomeGoalsHeartHomeostasisHuman PathologyImageInstructionKineticsLateralLesionMechanicsMolecularMolecular ProbesMorphogenesisMotorMovementMutationMyosin ATPaseMyosin S-2Neural tubePalatePhenotypePhylogenyPositioning AttributePredispositionProcessProteinsRNA SplicingRegulationResearchShapesSignal TransductionSpinal DysraphismSumThermodynamicsTissuesWorkbiophysical techniquesdesignflyforward geneticsgastrulationgene productimaging geneticsinsightinterdisciplinary approachinterestmutantresiliencereverse geneticsstomach cardiatransmission processwoundwound healing
中文摘要
细胞片的形态发生对后生动物的发育和动物形态的动态平衡至关重要
英文摘要
Cell sheet morphogenesis is essential for metazoan development and homeostasis of animal form – it contributes
to development, such as in gastrulation, neural tube, heart and palate formation and to homeostasis, in wound
healing. Gene expression and signaling cascades coordinate and regulate the cellular machines that drive
morphogenesis. Disfunction in these components causes developmental and wound healing defects that can
disfigure or kill. We focus on the molecular mechanisms of cell sheet morphogenesis during dorsal closure (DC)
in Drosophila melanogaster. During DC, lateral epidermal sheets advance to close a dorsal opening. We
pioneered the study of DC as a model system and use an unusually diverse repertoire of interdisciplinary
approaches, including live imaging, reverse and forward genetics and biophysical strategies to interrogate the
mechanics and regulation of closure in wild type and mutant embryos. We found that DC is the sum of four major
dynamic processes and is robust and resilient – no single force that drives closure is absolutely required.
Processes that contribute to DC at the molecular, cellular and tissue scales are highly conserved in animal
phylogeny making Drosophila an ideal model system for interrogating the molecular basis of morphogenesis.
There remain significant gaps in our understanding of this conceptually simple, yet biologically complex cell
sheet movement. To identify new “DC genes”, i.e., genes that when deleted, disrupt closure, we initiated a forward
genetic, live-imaging, screen. This screen used 194 deficiency stocks (Dfs) that collectively delete 5,778 of the
5,854 genes on melanogaster's 2nd chromosome. We have begun to extend our screen to the 3rd chromosome.
Remarkably, 96 Dfs caused notable and diverse defects in closure, indicating that a large number of discrete
biological processes contribute to closure and are susceptible to mutational disruption. Thus far, we have
identified 13 new pre-DC or DC genes that are responsible for the DC Df phenotypes. When extended to the whole
fly genome our screen is projected to identify ~165 new DC genes (only ~140 DC genes were known at the start
of our screen). Based on phenotype, we prioritize the DC Dfs on which to focus, identify the DC genes responsible
for their Df phenotypes, then characterize how the new DC gene products contribute to closure. A priority is to
understand the molecular mechanisms by which cell-cell interactions and cell-matrix based adhesion couple to
the actomyosin cytoskeleton – these connections must be robust enough to transmit forces, yet malleable enough
to allow the cell shape changes that define morphogenesis. Of further interest is a new effort to
thermodynamically and kinetically characterize the myosin 2 motor that drives morphogenesis in DC and other
developmental processes. Our goal is to assess how differential splicing that encodes myosin's motor domain
contributes to morphogenesis as a fast moving, slow/efficient force holding, strain sensing, or processive motor.
We are uniquely positioned to address the molecular and biophysical mechanisms that underlie the basic biology
of cell sheet morphogenesis in flies, research that directly informs vertebrate development and wound healing.
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Identifying Genetic Players in Cell Sheet Morphogenesis Using a Drosophila Deficiency Screen for Genes on Chromosome 2R Involved in Dorsal Closure.
使用果蝇缺陷筛选 2R 号染色体上参与背侧闭合的基因来识别细胞片形态发生中的遗传因素。
DOI:
10.1534/g3.118.200233
发表时间:
2018
期刊:
G3 (Bethesda, Md.)
影响因子:
--
作者:
[Mortensen,RichardD, Moore,ReganP, Fogerson,StephanieM, Chiou,HellenY, Obinero,ChimdinduV, Prabhu,NeelK, Wei,AngelaH, Crawford,JaniceM, Kiehart,DanielP]
通讯作者:
Kiehart,DanielP
DOI:
10.1091/mbc.e21-11-0537
发表时间:
2022-09-15
期刊:
MOLECULAR BIOLOGY OF THE CELL
影响因子:
3.3
作者:
[Moore, Regan P., Fogerson, Stephanie M., Tulu, U. Serdar, Yu, Jason W., Cox, Amanda H., Sican, Melissa A., Li, Dong, Legant, Wesley R., Weigel, Aubrey, V, Crawford, Janice M., Betzig, Eric, Kiehart, Daniel P.]
通讯作者:
Kiehart, Daniel P.
DOI:
10.1534/g3.120.401386
发表时间:
2020-11-05
期刊:
G3 (Bethesda, Md.)
影响因子:
--
作者:
[Fogerson SM, Mortensen RD, Moore RP, Chiou HY, Prabhu NK, Wei AH, Tsai D, Jadi O, Andoh-Baidoo K, Crawford J, Mudziviri M, Kiehart DP]
通讯作者:
Kiehart DP
Mutations in Drosophila crinkled/Myosin VIIA disrupt denticle morphogenesis.
果蝇皱纹/肌球蛋白VIIA 的突变破坏了小齿的形态发生。
DOI:
10.1016/j.ydbio.2020.11.007
发表时间:
2021-03
期刊:
Developmental biology
影响因子:
2.7
作者:
[Sallee JL, Crawford JM, Singh V, Kiehart DP]
通讯作者:
Kiehart DP
Wound repair in sea urchin larvae involves pigment cells and blastocoelar cells.
海胆幼虫的伤口修复涉及色素细胞和胚泡细胞。
DOI:
10.1016/j.ydbio.2022.08.005
发表时间:
2022-11
期刊:
DEVELOPMENTAL BIOLOGY
影响因子:
2.7
作者:
[Allen, Raymond L., George, Andrew N., Miranda, Esther, Phillips, Taji M., Crawford, Janice M., Kiehart, Daniel P., McClay, David R.]
通讯作者:
McClay, David R.
共 7 条
Morphogenesis: Biophysics and Genetics of Dorsal Closure
-
批准号:10200838
-
项目类别:
-
资助金额:$43.61万
-
财政年份:2018
-
负责人:DANIEL PETER KIEHART
-
依托单位:
Morphogenesis: Biophysics and Genetics of Dorsal Closure
-
批准号:10441492
-
项目类别:
-
资助金额:$43.57万
-
财政年份:2018
-
负责人:DANIEL PETER KIEHART
-
依托单位:
Design and Implementation of Genetically Encoded Myosin Based Force Sensors
-
批准号:8446280
-
项目类别:
-
资助金额:$18.38万
-
财政年份:2012
-
负责人:DANIEL PETER KIEHART
-
依托单位:
Design and Implementation of Genetically Encoded Myosin Based Force Sensors
-
批准号:8320666
-
项目类别:
-
资助金额:$21.88万
-
财政年份:2012
-
负责人:DANIEL PETER KIEHART
-
依托单位:
Morphogenesis: Biophysics and Genetics of Dorsal Closure
-
批准号:7923503
-
项目类别:
-
资助金额:$28.75万
-
财政年份:2009
-
负责人:DANIEL PETER KIEHART
-
依托单位:
Myosins VIIA, VIIB & XV in Fly Hearing and Morphogenesis
-
批准号:7252027
-
项目类别:
-
资助金额:$33.03万
-
财政年份:2005
-
负责人:DANIEL PETER KIEHART
-
依托单位:
Myosins VIIA, VIIB & XV in Fly Hearing and Morphogenesis
-
批准号:6964907
-
项目类别:
-
资助金额:$35.35万
-
财政年份:2005
-
负责人:DANIEL PETER KIEHART
-
依托单位:
Myosins VIIA, VIIB & XV in Fly Hearing and Morphogenesis
-
批准号:7640647
-
项目类别:
-
资助金额:$32.39万
-
财政年份:2005
-
负责人:DANIEL PETER KIEHART
-
依托单位:
Myosins VIIA, VIIB & XV in Fly Hearing and Morphogenesis
-
批准号:7456402
-
项目类别:
-
资助金额:$32.5万
-
财政年份:2005
-
负责人:DANIEL PETER KIEHART
-
依托单位:
Myosins VIIA, VIIB & XV in Fly Hearing and Morphogenesis
-
批准号:7094070
-
项目类别:
-
资助金额:$34.12万
-
财政年份:2005
-
负责人:DANIEL PETER KIEHART
-
依托单位:
MOLECULAR GENETIC ANALYSIS OF WOUND HEALING--DROSOPHILA
-
批准号:6387149
-
项目类别:
-
资助金额:$23.1万
-
财政年份:2000
-
负责人:DANIEL PETER KIEHART
-
依托单位:
MOLECULAR GENETIC ANALYSIS OF WOUND HEALING--DROSOPHILA
-
批准号:6090924
-
项目类别:
-
资助金额:$28.44万
-
财政年份:2000
-
负责人:DANIEL PETER KIEHART
-
依托单位:
MOLECULAR GENETIC ANALYSIS OF WOUND HEALING--DROSOPHILA
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批准号:6526080
-
项目类别:
-
资助金额:$23.1万
-
财政年份:2000
-
负责人:DANIEL PETER KIEHART
-
依托单位:
CYTOPLASMIC MYOSIN FUNCTION IN VITRO
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批准号:2177155
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项目类别:
-
资助金额:$28.77万
-
财政年份:1984
-
负责人:DANIEL PETER KIEHART
-
依托单位:
CYTOPLASMIC MYOSIN FUNCTION IN VITRO
-
批准号:2770930
-
项目类别:
-
资助金额:$27.04万
-
财政年份:1984
-
负责人:DANIEL PETER KIEHART
-
依托单位:
CYTOPLASMIC MYOSIN FUNCTION IN VITRO AND IN VIVO
-
批准号:3283907
-
项目类别:
-
资助金额:$1.41万
-
财政年份:1984
-
负责人:DANIEL PETER KIEHART
-
依托单位:
CYTOPLASMIC MYOSIN FUNCTION IN VITRO AND IN VIVO
-
批准号:3283910
-
项目类别:
-
资助金额:$20.36万
-
财政年份:1984
-
负责人:DANIEL PETER KIEHART
-
依托单位:
CYTOPLASMIC MYOSIN FUNCTION IN VITRO AND IN VIVO
-
批准号:3283906
-
项目类别:
-
资助金额:$30.7万
-
财政年份:1984
-
负责人:DANIEL PETER KIEHART
-
依托单位:
CYTOPLASMIC MYOSIN FUNCTION IN VITRO AND IN VIVO
-
批准号:3283911
-
项目类别:
-
资助金额:$19.53万
-
财政年份:1984
-
负责人:DANIEL PETER KIEHART
-
依托单位:
Morphogenesis Biophysics and Genetics of Dorsal Closure
-
批准号:6936536
-
项目类别:
-
资助金额:$43.54万
-
财政年份:1984
-
负责人:DANIEL PETER KIEHART
-
依托单位:
海外基金