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A New Model: The Mammalian Brain is Derived from Two Separate Regional Progenitors
A New Model: The Mammalian Brain is Derived from Two Separate Regional Progenitors
A New Model: The Mammalian Brain is Derived from Two Separate Regional Progenitors

상세정보

자료유형  
 학위논문 서양
최종처리일시  
20260202105620
ISBN  
9798265428516
DDC  
574
저자명  
Dundes, Carolyn Elizabeth.
서명/저자  
A New Model: The Mammalian Brain is Derived from Two Separate Regional Progenitors
발행사항  
[Sl] : Stanford University, 2023
발행사항  
Ann Arbor : ProQuest Dissertations & Theses, 2023
형태사항  
141 p
주기사항  
Source: Dissertations Abstracts International, Volume: 87-05, Section: B.
주기사항  
Advisor: Loh, Kyle.
학위논문주기  
Thesis (Ph.D.)--Stanford University, 2023.
초록/해제  
요약The mammalian brain is a truly remarkable organ, and its mature form is the culmination of a complex sequence of developmental biology. A key component of this complexity lies in the fact that the brain is not a homogeneous tissue, but rather a modular system with distinct sub-regions that work in close concert with one another. In the developing organism, the first identifiable brain sub-regions are the forebrain, midbrain, and hindbrain. All sub-regions of the brain are derived from the ectoderm germ layer of the embryo, yet the precise embryonic cues for inducing these regions, and the developmental timing of those cues, remains incompletely understood. In this thesis, I have employed two complementary approaches to elucidate the first steps of brain development and subregional patterning. First, I used mouse embryonic lineage tracing to label and follow populations of cells in the neural ectoderm in vivo. I found that cells labeled in the posterior domains of mouse gastrula-stage embryos exclusively gave rise to the hindbrain, but not forebrain or midbrain. These data revealed that regional identity may be established concomitantly with neural identity. Second, I used human pluripotent stem cells (hPSCs, which have the developmental potential to become any cell in the body) to precisely determine the sequence of signals required to generate embryonic forebrain, midbrain, and hindbrain. Surprisingly, hPSC-derived anterior neural ectoderm (aNE) was restricted to generate forebrain and midbrain, and hPSC-derived posterior neural ectoderm (pNE) was restricted to hindbrain fates, consistent with my in vivo data. I thus propose a revised model of brain development in which the neural ectoderm is already restricted to specific subregions of the brain, which has substantial implications for our ability to model human brain development using hPSCs.
일반주제명  
Hybridization
일반주제명  
Embryos
일반주제명  
Neurons
일반주제명  
Gene expression
일반주제명  
Stem cells
일반주제명  
Brain research
일반주제명  
Developmental biology
일반주제명  
Regenerative medicine
일반주제명  
Transcription factors
일반주제명  
Genetic engineering
일반주제명  
Bioinformatics
일반주제명  
Cellular biology
일반주제명  
Genetics
일반주제명  
Medicine
일반주제명  
Neurosciences
일반주제명  
Engineering
기타저자  
Stanford University.
기본자료저록  
Dissertations Abstracts International. 87-05B.
전자적 위치 및 접속  
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MARC

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■1001  ▼aDundes,  Carolyn  Elizabeth.
■24512▼aA  New  Model:  The  Mammalian  Brain  is  Derived  from  Two  Separate  Regional  Progenitors
■260    ▼a[Sl]▼bStanford  University▼c2023
■260  1▼aAnn  Arbor▼bProQuest  Dissertations  &  Theses▼c2023
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■500    ▼aSource:  Dissertations  Abstracts  International,  Volume:  87-05,  Section:  B.
■500    ▼aAdvisor:  Loh,  Kyle.
■5021  ▼aThesis  (Ph.D.)--Stanford  University,  2023.
■520    ▼aThe  mammalian  brain  is  a  truly  remarkable  organ,  and  its  mature  form  is  the  culmination  of  a  complex  sequence  of  developmental  biology.  A  key  component  of  this  complexity  lies  in  the  fact  that  the  brain  is  not  a  homogeneous  tissue,  but  rather  a  modular  system  with  distinct  sub-regions  that  work  in  close  concert  with  one  another.  In  the  developing  organism,  the  first  identifiable  brain  sub-regions  are  the  forebrain,  midbrain,  and  hindbrain.  All  sub-regions  of  the  brain  are  derived  from  the  ectoderm  germ  layer  of  the  embryo,  yet  the  precise  embryonic  cues  for  inducing  these  regions,  and  the  developmental  timing  of  those  cues,  remains  incompletely  understood.  In  this  thesis,  I  have  employed  two  complementary  approaches  to  elucidate  the  first  steps  of  brain  development  and  subregional  patterning.  First,  I  used  mouse  embryonic  lineage  tracing  to  label  and  follow  populations  of  cells  in  the  neural  ectoderm  in  vivo.  I  found  that  cells  labeled  in  the  posterior  domains  of  mouse  gastrula-stage  embryos  exclusively  gave  rise  to  the  hindbrain,  but  not  forebrain  or  midbrain.  These  data  revealed  that  regional  identity  may  be  established  concomitantly  with  neural  identity.  Second,  I  used  human  pluripotent  stem  cells  (hPSCs,  which  have  the  developmental  potential  to  become  any  cell  in  the  body)  to  precisely  determine  the  sequence  of  signals  required  to  generate  embryonic  forebrain,  midbrain,  and  hindbrain.  Surprisingly,  hPSC-derived  anterior  neural  ectoderm  (aNE)  was  restricted  to  generate  forebrain  and  midbrain,  and  hPSC-derived  posterior  neural  ectoderm  (pNE)  was  restricted  to  hindbrain  fates,  consistent  with  my  in  vivo  data.  I  thus  propose  a  revised  model  of  brain  development  in  which  the  neural  ectoderm  is  already  restricted  to  specific  subregions  of  the  brain,  which  has  substantial  implications  for  our  ability  to  model  human  brain  development  using  hPSCs.
■590    ▼aSchool  code:  0212.
■650  4▼aHybridization
■650  4▼aEmbryos
■650  4▼aNeurons
■650  4▼aGene  expression
■650  4▼aStem  cells
■650  4▼aBrain  research
■650  4▼aDevelopmental  biology
■650  4▼aRegenerative  medicine
■650  4▼aTranscription  factors
■650  4▼aGenetic  engineering
■650  4▼aBioinformatics
■650  4▼aCellular  biology
■650  4▼aGenetics
■650  4▼aMedicine
■650  4▼aNeurosciences
■650  4▼aEngineering
■690    ▼a0758
■690    ▼a0715
■690    ▼a0379
■690    ▼a0369
■690    ▼a0564
■690    ▼a0317
■690    ▼a0537
■71020▼aStanford  University.
■7730  ▼tDissertations  Abstracts  International▼g87-05B.
■790    ▼a0212
■791    ▼aPh.D.
■792    ▼a2023
■793    ▼aEnglish
■85640▼uhttp://www.riss.kr/pdu/ddodLink.do?id=T17360793▼nKERIS▼z이  자료의  원문은  한국교육학술정보원에서  제공합니다.

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