東華大學圖書館 |

Surface Behaviors in Development: Pattern Formation in the Cell Cortex and Nuclear Envelope.

紀錄類型:	書目-電子資源 : Monograph/item
正題名/作者:	Surface Behaviors in Development: Pattern Formation in the Cell Cortex and Nuclear Envelope./
作者:	Jackson, Jonathan A.
出版者:	Ann Arbor : ProQuest Dissertations & Theses, : 2023,
面頁冊數:	202 p.
附註:	Source: Dissertations Abstracts International, Volume: 85-09, Section: B.
Contained By:	Dissertations Abstracts International85-09B.
標題:	Biophysics. -
電子資源:	https://pqdd.sinica.edu.tw/twdaoapp/servlet/advanced?query=30988849
ISBN:	9798381947748

Surface Behaviors in Development: Pattern Formation in the Cell Cortex and Nuclear Envelope.
Jackson, Jonathan A.

Surface Behaviors in Development: Pattern Formation in the Cell Cortex and Nuclear Envelope. - Ann Arbor : ProQuest Dissertations & Theses, 2023 - 202 p.

Source: Dissertations Abstracts International, Volume: 85-09, Section: B.

Thesis (Ph.D.)--Harvard University, 2023.

The shaping of biological systems into the forms required for their function requires a complex interplay of force generation and response, genetics, biochemical signaling, and geometrical cues. Morphogenetic processes unfold across wide-ranging spatial and temporal scales, further requiring tightly regulated feedback mechanisms connecting diverse components at different organizational levels. This dissertation addresses some mechanisms through which biological surfaces generate and respond to forces during development of the fruit fly Drosophila melanogaster, as well as the role of regulatory proteins and feedback loops in one of the main force-generating signaling pathways in the actomyosin cortex.First, we characterized the shape of nuclear envelopes in female germline cells in the Drosophila melanogaster egg chamber, quantifying the appearance and progressive amplitude increase of fluctuating wrinkles in the envelope. We showed these amplitudes scale in a manner consistent with predictions from a model of a thin elastic shell subject to fluctuating loads. We further showed wrinkle amplitude is reduced upon reduction in cytoplasmic fluctuations following microtubule disruption, and we found a decrease in Lamin C concentration in the nuclear envelope during development that accompanies the increase in wrinkle amplitude.Next, we focused on the dynamics of intercellular transport of contents from support germline cells to the oocyte in a process known as 'nurse cell dumping' that occurs during late oogenesis. We found that this large-scale fluid transport process, required to provide the oocyte with sufficient nutrients to support early embryonic development, unfolds in two phases, with changes in actomyosin behavior only required for the latter phase. The first phase instead relies on a cell-size gradient in the support cells that sets up a pressure gradient to drive fluid between cells into the oocyte in a reproducible order. The order and timescale of transport match predictions from a model based on a modified form of the Young-Laplace law applied to the sixteen-cell network. The second phase of transport requires traveling waves of actomyosin contractility, with directionality and completeness of transport reduced upon perturbation of wave behavior induced by knockdown of RhoGAP15B, a negative regulator of the small GTPase RhoA.Finally, we investigated the connection between availability of RhoA regulators and the down-stream patterns of cortical actomyosin contractility in space and time. Building on results from the second phase of nurse cell dumping, we identified a RhoGEF, Pbl/Ect2, required for proper regulation of actomyosin waves and complete nurse cell dumping. We showed that, prior to wave onset, Ect2 and RhoGAP15B exit the nucleus and accumulate at the nurse cell cortex in an order matching the order of wave onset, suggesting simultaneous increase of both RhoGEF and RhoGAP might induce waves. We tested this hypothesis in the early Drosophila embryo, showing that overexpression of a different RhoGEF/RhoGAP pair converts actomyosin from the pulsatile behavior that usually occurs in this system to traveling waves. This result further suggests increased RhoGEF and RhoGAP together induce wave onset in the actomyosin cortex, a finding consistent with recent work in the oocytes of starfish and Xenopus.Taken together, our results from the first chapter shed light on how properties of the nuclear membrane shape its response to external forces during development. The second and third chapters provide insight into how feedback loops in the RhoA system affect patterns of force production in individual cell cortices that must be coupled to produce tissue-level shape changes. Additionally, the results presented here provide further examples of how developmental processes depend on the interplay of biological and physical mechanisms.

ISBN: 9798381947748Subjects--Topical Terms:

518360
Biophysics.
Subjects--Index Terms:

Biological systems

Surface Behaviors in Development: Pattern Formation in the Cell Cortex and Nuclear Envelope.
LDR:05065nmm a2200385 4500 001 2399953
005 20240916070028.5
006 m o d
007 cr#unu||||||||
008 251215s2023 ||||||||||||||||| ||eng d
020 $a 9798381947748
035 $a (MiAaPQ)AAI30988849
035 $a AAI30988849
040 $a MiAaPQ $c MiAaPQ
100 1 $a Jackson, Jonathan A. $0 (orcid)0000-0001-5051-1499 $3 3769924
245 1 0 $a Surface Behaviors in Development: Pattern Formation in the Cell Cortex and Nuclear Envelope.
260 1 $a Ann Arbor : $b ProQuest Dissertations & Theses, $c 2023
300 $a 202 p.
500 $a Source: Dissertations Abstracts International, Volume: 85-09, Section: B.
500 $a Advisor: Martin, Adam C.
502 $a Thesis (Ph.D.)--Harvard University, 2023.
520 $a The shaping of biological systems into the forms required for their function requires a complex interplay of force generation and response, genetics, biochemical signaling, and geometrical cues. Morphogenetic processes unfold across wide-ranging spatial and temporal scales, further requiring tightly regulated feedback mechanisms connecting diverse components at different organizational levels. This dissertation addresses some mechanisms through which biological surfaces generate and respond to forces during development of the fruit fly Drosophila melanogaster, as well as the role of regulatory proteins and feedback loops in one of the main force-generating signaling pathways in the actomyosin cortex.First, we characterized the shape of nuclear envelopes in female germline cells in the Drosophila melanogaster egg chamber, quantifying the appearance and progressive amplitude increase of fluctuating wrinkles in the envelope. We showed these amplitudes scale in a manner consistent with predictions from a model of a thin elastic shell subject to fluctuating loads. We further showed wrinkle amplitude is reduced upon reduction in cytoplasmic fluctuations following microtubule disruption, and we found a decrease in Lamin C concentration in the nuclear envelope during development that accompanies the increase in wrinkle amplitude.Next, we focused on the dynamics of intercellular transport of contents from support germline cells to the oocyte in a process known as 'nurse cell dumping' that occurs during late oogenesis. We found that this large-scale fluid transport process, required to provide the oocyte with sufficient nutrients to support early embryonic development, unfolds in two phases, with changes in actomyosin behavior only required for the latter phase. The first phase instead relies on a cell-size gradient in the support cells that sets up a pressure gradient to drive fluid between cells into the oocyte in a reproducible order. The order and timescale of transport match predictions from a model based on a modified form of the Young-Laplace law applied to the sixteen-cell network. The second phase of transport requires traveling waves of actomyosin contractility, with directionality and completeness of transport reduced upon perturbation of wave behavior induced by knockdown of RhoGAP15B, a negative regulator of the small GTPase RhoA.Finally, we investigated the connection between availability of RhoA regulators and the down-stream patterns of cortical actomyosin contractility in space and time. Building on results from the second phase of nurse cell dumping, we identified a RhoGEF, Pbl/Ect2, required for proper regulation of actomyosin waves and complete nurse cell dumping. We showed that, prior to wave onset, Ect2 and RhoGAP15B exit the nucleus and accumulate at the nurse cell cortex in an order matching the order of wave onset, suggesting simultaneous increase of both RhoGEF and RhoGAP might induce waves. We tested this hypothesis in the early Drosophila embryo, showing that overexpression of a different RhoGEF/RhoGAP pair converts actomyosin from the pulsatile behavior that usually occurs in this system to traveling waves. This result further suggests increased RhoGEF and RhoGAP together induce wave onset in the actomyosin cortex, a finding consistent with recent work in the oocytes of starfish and Xenopus.Taken together, our results from the first chapter shed light on how properties of the nuclear membrane shape its response to external forces during development. The second and third chapters provide insight into how feedback loops in the RhoA system affect patterns of force production in individual cell cortices that must be coupled to produce tissue-level shape changes. Additionally, the results presented here provide further examples of how developmental processes depend on the interplay of biological and physical mechanisms.
590 $a School code: 0084.
650 4 $a Biophysics. $3 518360
650 4 $a Cellular biology. $3 3172791
650 4 $a Developmental biology. $3 592588
650 4 $a Biology. $3 522710
653 $a Biological systems
653 $a Drosophila melanogaster
653 $a Physical mechanisms
653 $a Germline cells
690 $a 0786
690 $a 0379
690 $a 0758
690 $a 0306
710 2 $a Harvard University. $b Biophysics. $3 3174713
773 0 $t Dissertations Abstracts International $g 85-09B.
790 $a 0084
791 $a Ph.D.
792 $a 2023
793 $a English
856 4 0 $u https://pqdd.sinica.edu.tw/twdaoapp/servlet/advanced?query=30988849