A new model : the mammalian brain is derived from two separate regional progenitors
- The 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 sub-regional 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 sub-regions of the brain, which has substantial implications for our ability to model human brain development using hPSCs.
|Type of resource
|electronic resource; remote; computer; online resource
|1 online resource.
|Dundes, Carolyn Elizabeth
|Degree committee member
|Degree committee member
|Stanford University, School of Medicine
|Stanford University, Program in Stem Cell Biology and Regenerative Medicine
|Statement of responsibility
|Submitted to the Program in Stem Cell Biology and Regenerative Medicine.
|Thesis Ph.D. Stanford University 2023.
- © 2023 by Carolyn Elizabeth Dundes
- This work is licensed under a Creative Commons Attribution Non Commercial Share Alike 3.0 Unported license (CC BY-NC-SA).
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