Reverse-engineering organogenesis through feedback loops between model systems.

Biological complexity and ethical limitations necessitate models of human development. Traditionally, genetic model systems have provided inexpensive routes to define mechanisms governing organ development. Recent progress has led to 3D human organoid models of development and disease. However, robust methods to control the size and morphology of organoids for high throughput studies need to be developed. Additionally, insights from multiple developmental contexts are required to reveal conserved genes and processes regulating organ growth and development. Positive feedback between quantitative studies using mammalian organoids and insect micro-organs enable identification of underlying principles for organ size and shape control. Advances in the field of multicellular systems engineering are enabling unprecedented high-content studies in developmental biology and disease modeling. These will lead to fundamental advances in regenerative medicine and tissue-engineered soft robotics.

[1]  Youmin Hou,et al.  In Vitro Epithelial Organoid Generation Induced by Substrate Nanotopography , 2015, Scientific Reports.

[2]  Frank Jülicher,et al.  Interface Contractility between Differently Fated Cells Drives Cell Elimination and Cyst Formation , 2016, Current Biology.

[3]  Margaret Y. Nettleton,et al.  High throughput in vivo functional validation of candidate congenital heart disease genes in Drosophila , 2017, eLife.

[4]  M. Shuler.  Organ-, body- and disease-on-a-chip systems. , 2017, Lab on a chip.

[5]  H. Bellen,et al.  Building dialogues between clinical and biomedical research through cross-species collaborations. , 2017, Seminars in cell & developmental biology.

[6]  Jeremiah J. Zartman,et al.  Release of Applied Mechanical Loading Stimulates Intercellular Calcium Waves in Drosophila Wing Discs. , 2017, Biophysical journal.

[7]  G Wayne Brodland,et al.  How computational models can help unlock biological systems. , 2015, Seminars in cell & developmental biology.

[8]  M. Milner,et al.  The growth and differentiation in vitro of leg and wing imaginal disc cells from Drosophila melanogaster , 1988 .

[9]  N. Kamamichi,et al.  Earthworm muscle driven bio-micropump , 2017 .

[10]  G. Echalier.  Drosophila cells in culture , 1997 .

[11]  Yongmin Cho,et al.  Trends in high‐throughput and functional neuroimaging in Caenorhabditis elegans , 2017, Wiley interdisciplinary reviews. Systems biology and medicine.

[12]  P. Lawrence,et al.  Compartments in the wing of Drosophila: a study of the engrailed gene. , 1976, Developmental biology.

[13]  Gaudenz Danuser,et al.  Mechanical Feedback through E-Cadherin Promotes Direction Sensing during Collective Cell Migration , 2014, Cell.

[14]  S. Shvartsman,et al.  Unit operations of tissue development: epithelial folding. , 2010, Annual review of chemical and biomolecular engineering.

[15]  William McLamb,et al.  Multi-Organ toxicity demonstration in a functional human in vitro system composed of four organs , 2016, Scientific Reports.

[16]  Yoshiki Sasai,et al.  Self-formation of optic cups and storable stratified neural retina from human ESCs. , 2012, Cell stem cell.

[17]  H. Clevers,et al.  Intestinal epithelial organoids fuse to form self-organizing tubes in floating collagen gels , 2017, Development.

[18]  H. Richardson,et al.  An in vivo large-scale chemical screening platform using Drosophila for anti-cancer drug discovery , 2012, Disease Models & Mechanisms.

[19]  Madeline A. Lancaster,et al.  A Simple Method of Generating 3D Brain Organoids Using Standard Laboratory Equipment. , 2017, Methods in molecular biology.

[20]  Michael F. Wangler,et al.  Fruit Flies in Biomedical Research , 2015, Genetics.

[21]  Stefan R. Pulver,et al.  Genetically encoded calcium indicators for multi-color neural activity imaging and combination with optogenetics , 2013, Front. Mol. Neurosci..

[22]  J. B. Duffy,et al.  GAL4 system in drosophila: A fly geneticist's swiss army knife , 2002, Genesis.

[23]  W. Cho,et al.  Non-Invasive Screening for Alzheimer’s Disease by Sensing Salivary Sugar Using Drosophila Cells Expressing Gustatory Receptor (Gr5a) Immobilized on an Extended Gate Ion-Sensitive Field-Effect Transistor (EG-ISFET) Biosensor , 2015, PloS one.

[24]  Nick Barker,et al.  Organoids as an in vitro model of human development and disease , 2016, Nature Cell Biology.

[25]  C. Desplan,et al.  Power tools for gene expression and clonal analysis in Drosophila , 2011, Nature Methods.

[26]  L. Pick,et al.  Drosophila as a Model for Diabetes and Diseases of Insulin Resistance. , 2017, Current topics in developmental biology.

[27]  Takanori Takebe,et al.  Reverse engineering liver buds through self-driven condensation and organization towards medical application. , 2016, Developmental biology.

[28]  Ross L Cagan,et al.  Drosophila cancer models , 2012, Developmental dynamics : an official publication of the American Association of Anatomists.

[29]  Konrad Basler,et al.  A high-throughput template for optimizing Drosophila organ culture with response-surface methods , 2013, Development.

[30]  C. Ronco,et al.  Heart–kidney crosstalk and role of humoral signaling in critical illness , 2014, Critical Care.

[31]  Jeremiah J Zartman,et al.  Sizing it up: the mechanical feedback hypothesis of organ growth regulation. , 2014, Seminars in cell & developmental biology.

[32]  Qiang Liu,et al.  Organ-to-Organ Communication: A Drosophila Gastrointestinal Tract Perspective , 2017, Front. Cell Dev. Biol..

[33]  C. Nichols,et al.  Human Disease Models in Drosophila melanogaster and the Role of the Fly in Therapeutic Drug Discovery , 2011, Pharmacological Reviews.

[34]  A. Martinez Arias,et al.  Organoids and the genetically encoded self‐assembly of embryonic stem cells , 2015, BioEssays : news and reviews in molecular, cellular and developmental biology.

[35]  Madeline A. Lancaster,et al.  Probing human brain evolution and development in organoids. , 2017, Current opinion in cell biology.

[36]  K. Basler,et al.  Dpp controls growth and patterning in Drosophila wing precursors through distinct modes of action , 2017, eLife.

[37]  H. Clevers,et al.  Organoid biobanking: identifying the ethics , 2016, EMBO reports.

[38]  I. Hariharan,et al.  Organ Size Control: Lessons from Drosophila. , 2015, Developmental cell.

[39]  T. Adachi,et al.  Self-organizing optic-cup morphogenesis in three-dimensional culture , 2011, Nature.

[40]  F. J. Livesey,et al.  Guided self-organization and cortical plate formation in human brain organoids , 2017, Nature Biotechnology.

[41]  G. Morata,et al.  Developmental compartmentalisation of the wing disk of Drosophila. , 1973, Nature: New biology.

[42]  Jacob W. Guggenheim,et al.  A process engineering approach to increase organoid yield , 2017, Development.

[43]  Hans Clevers,et al.  Modeling Development and Disease with Organoids , 2016, Cell.

[44]  Hans Clevers,et al.  CRISPR/Cas 9 genome editing and its applications in organoids. , 2017, American journal of physiology. Gastrointestinal and liver physiology.

[45]  Subash C. Gupta,et al.  Cancer Drug Development Using Drosophila as an in vivo Tool: From Bedside to Bench and Back. , 2016, Trends in pharmacological sciences.

[46]  T. Bowman,et al.  Tissue-Specific Progenitor and Stem Cells Concise Review : Hematopoietic Stem Cell Origins : Lessons From Embryogenesis for Improving Regenerative Medicine , 2017 .

[47]  T. Rodríguez,et al.  Cancer: The Transforming Power of Cell Competition , 2016, Current Biology.

[48]  David W. Nauen,et al.  Brain-Region-Specific Organoids Using Mini-bioreactors for Modeling ZIKV Exposure , 2016, Cell.

[49]  G. Morata,et al.  Cell competition, growth and size control in the Drosophila wing imaginal disc , 2009, Development.

[50]  Chaenyung Cha,et al.  Tailoring hydrogel adhesion to polydimethylsiloxane substrates using polysaccharide glue. , 2013, Angewandte Chemie.

[51]  C. Yeh,et al.  Self-organization process in newborn skin organoid formation inspires strategy to restore hair regeneration of adult cells , 2017, Proceedings of the National Academy of Sciences.

[52]  Takayuki Hoshino,et al.  Atmospheric-operable bioactuator powered by insect muscle packaged with medium. , 2013, Lab on a chip.

[53]  UesugiKaoru,et al.  Contractile Performance and Controllability of Insect Muscle-Powered Bioactuator with Different Stimulation Strategies for Soft Robotics , 2016 .

[54]  R. Paro,et al.  The legacy of Drosophila imaginal discs , 2016, Chromosoma.

[55]  Stanislav Y Shvartsman,et al.  The Spatiotemporal Limits of Developmental Erk Signaling. , 2017, Developmental cell.

[56]  Joseph R Ecker,et al.  Cerebral Organoids Recapitulate Epigenomic Signatures of the Human Fetal Brain. , 2016, Cell reports.

[57]  J. Bagley,et al.  Fused cerebral organoids model interactions between brain regions , 2017, Nature Methods.

[58]  J. C. Pastor-Pareja,et al.  Basement Membrane Manipulation in Drosophila Wing Discs Affects Dpp Retention but Not Growth Mechanoregulation. , 2017, Developmental cell.

[59]  Hanry Yu,et al.  Towards a human-on-chip: culturing multiple cell types on a chip with compartmentalized microenvironments. , 2009, Lab on a chip.

[60]  Zhiliang Xu,et al.  Multi-scale computational study of the mechanical regulation of cell mitotic rounding in epithelia , 2017, bioRxiv.

[61]  H. Nijhout,et al.  Bombyxin is a growth factor for wing imaginal disks in Lepidoptera , 2002, Proceedings of the National Academy of Sciences of the United States of America.

[62]  Azzam,et al.  Drosophila melanogaster: Deciphering Alzheimer's Disease. , 2017, The Malaysian journal of medical sciences : MJMS.

[63]  M. Sur,et al.  Induction of Expansion and Folding in Human Cerebral Organoids. , 2017, Cell stem cell.

[64]  J. Juang,et al.  Infection-induced intestinal oxidative stress triggers organ-to-organ immunological communication in Drosophila. , 2012, Cell host & microbe.

[65]  M. Boutros,et al.  Oxygenation and adenosine deaminase support growth and proliferation of ex vivo cultured Drosophila wing imaginal discs , 2017, Development.

[66]  Pierre-François Lenne,et al.  Local and tissue-scale forces drive oriented junction growth during tissue extension , 2015, Nature Cell Biology.

[67]  Takanori Takebe,et al.  Vascularized and Complex Organ Buds from Diverse Tissues via Mesenchymal Cell-Driven Condensation. , 2015, Cell stem cell.