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Cite this page: Hill, M.A. (2020, January 22) Embryology Molecular Development. Retrieved from https://embryology.med.unsw.edu.au/embryology/index.php/Talk:Molecular_Development
Chen X, Ke Y, Wu K, Zhao H, Sun Y, Gao L, Liu Z, Zhang J, Tao W, Hou Z, Liu H, Liu J & Chen ZJ. (2019). Key role for CTCF in establishing chromatin structure in human embryos. Nature , , . PMID: 31801998 DOI.
Key role for CTCF in establishing chromatin structure in human embryos.
Abstract In the interphase of the cell cycle, chromatin is arranged in a hierarchical structure within the nucleus1,2, which has an important role in regulating gene expression3-6. However, the dynamics of 3D chromatin structure during human embryogenesis remains unknown. Here we report that, unlike mouse sperm, human sperm cells do not express the chromatin regulator CTCF and their chromatin does not contain topologically associating domains (TADs). Following human fertilization, TAD structure is gradually established during embryonic development. In addition, A/B compartmentalization is lost in human embryos at the 2-cell stage and is re-established during embryogenesis. Notably, blocking zygotic genome activation (ZGA) can inhibit TAD establishment in human embryos but not in mouse or Drosophila. Of note, CTCF is expressed at very low levels before ZGA, and is then highly expressed at the ZGA stage when TADs are observed. TAD organization is significantly reduced in CTCF knockdown embryos, suggesting that TAD establishment during ZGA in human embryos requires CTCF expression. Our results indicate that CTCF has a key role in the establishment of 3D chromatin structure during human embryogenesis.
Little DR, Gerner-Mauro KN, Flodby P, Crandall ED, Borok Z, Akiyama H, Kimura S, Ostrin EJ & Chen J. (2019). Transcriptional control of lung alveolar type 1 cell development and maintenance by NK homeobox 2-1. Proc. Natl. Acad. Sci. U.S.A. , 116, 20545-20555. PMID: 31548395 DOI.
Abstract The extraordinarily thin alveolar type 1 (AT1) cell constitutes nearly the entire gas exchange surface and allows passive diffusion of oxygen into the blood stream. Despite such an essential role, the transcriptional network controlling AT1 cells remains unclear. Using cell-specific knockout mouse models, genomic profiling, and 3D imaging, we found that NK homeobox 2-1 (Nkx2-1) is expressed in AT1 cells and is required for the development and maintenance of AT1 cells. Without Nkx2-1, developing AT1 cells lose 3 defining features-molecular markers, expansive morphology, and cellular quiescence-leading to alveolar simplification and lethality. NKX2-1 is also cell-autonomously required for the same 3 defining features in mature AT1 cells. Intriguingly, Nkx2-1 mutant AT1 cells activate gastrointestinal (GI) genes and form dense microvilli-like structures apically. Single-cell RNA-seq supports a linear transformation of Nkx2-1 mutant AT1 cells toward a GI fate. Whole lung ChIP-seq shows NKX2-1 binding to 68% of genes that are down-regulated upon Nkx2-1 deletion, including 93% of known AT1 genes, but near-background binding to up-regulated genes. Our results place NKX2-1 at the top of the AT1 cell transcriptional hierarchy and demonstrate remarkable plasticity of an otherwise terminally differentiated cell type. KEYWORDS: NK homeobox 2-1; alveolar type 1 cell; alveologenesis; lung development; transcriptional control PMID: 31548395 PMCID: PMC6789920 [Available on 2020-03-23] DOI: 10.1073/pnas.1906663116
Topology of mammalian developmental enhancers and their regulatory landscapes
Nature. 2013 Oct 24;502(7472):499-506. doi: 10.1038/nature12753.
de Laat W1, Duboule D. Author information
How a complex animal can arise from a fertilized egg is one of the oldest and most fascinating questions of biology, the answer to which is encoded in the genome. Body shape and organ development, and their integration into a functional organism all depend on the precise expression of genes in space and time. The orchestration of transcription relies mostly on surrounding control sequences such as enhancers, millions of which form complex regulatory landscapes in the non-coding genome. Recent research shows that high-order chromosome structures make an important contribution to enhancer functionality by triggering their physical interactions with target genes.
Left–right asymmetry: cilia stir up new surprises in the node
developmental genetic regulatory networks
Pattern, growth, and control
Cell. 2011 Mar 18;144(6):955-69.
Lander AD. Source Department of Developmental and Cell Biology, Center for Complex Biological Systems, University of California, Irvine, Irvine, CA 92697-2300, USA. email@example.com
Systems biology seeks not only to discover the machinery of life but to understand how such machinery is used for control, i.e., for regulation that achieves or maintains a desired, useful end. This sort of goal-directed, engineering-centered approach also has deep historical roots in developmental biology. Not surprisingly, developmental biology is currently enjoying an influx of ideas and methods from systems biology. This Review highlights current efforts to elucidate design principles underlying the engineering objectives of robustness, precision, and scaling as they relate to the developmental control of growth and pattern formation. Examples from vertebrate and invertebrate development are used to illustrate general lessons, including the value of integral feedback in achieving set-point control; the usefulness of self-organizing behavior; the importance of recognizing and appropriately handling noise; and the absence of "free lunch." By illuminating such principles, systems biology is helping to create a functional framework within which to make sense of the mechanistic complexity of organismal development. Copyright © 2011 Elsevier Inc. All rights reserved.
I am 2.85 billion nucleotides of DNA, but so is a chimpanzee, and all this DNA encodes only about 20,000-25,000 protein-coding genes.
In development, I am not that different from a mouse or a fly and many of the signals that regulate development are used time and time again.
We have come a long way from just observing development to now wanting to understand how the complex program of development is controlled. Using new research tools and some excellent animal models researchers have discovered common themes and mechanisms that tie all embryonic development together.
Molecular mechanisms of development is an exciting area and requires a variety of different skills. This page introduces only a few examples and should give you a feel for the topic. Note that each section of system notes has a page covering molecular Development in that system.