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Tridimensional Visualization and Analysis of Early Human Development.

Cell | 2017

Generating a precise cellular and molecular cartography of the human embryo is essential to our understanding of the mechanisms of organogenesis in normal and pathological conditions. Here, we have combined whole-mount immunostaining, 3DISCO clearing, and light-sheet imaging to start building a 3D cellular map of the human development during the first trimester of gestation. We provide high-resolution 3D images of the developing peripheral nervous, muscular, vascular, cardiopulmonary, and urogenital systems. We found that the adult-like pattern of skin innervation is established before the end of the first trimester, showing important intra- and inter-individual variations in nerve branches. We also present evidence for a differential vascularization of the male and female genital tracts concomitant with sex determination. This work paves the way for a cellular and molecular reference atlas of human cells, which will be of paramount importance to understanding human development in health and disease. PAPERCLIP.

Pubmed ID: 28340341 RIS Download

Mesh terms: Embryo, Mammalian | Embryonic Development | Fetus | Human Development | Humans | Imaging, Three-Dimensional | Immunohistochemistry | Microscopy | Organogenesis | Peripheral Nervous System

Research resources used in this publication

Additional research tools detected in this publication

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Antibodies used in this publication

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Monoclonal Anti-Myosin (Skeletal, Fast) antibody produced in mouse (antibody)

RRID:AB_477190

This monoclonal antibody targets Myosin (Skeletal Fast) antibody produced in mouse

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Mouse/Rat Contactin-2/TAG1 Affinity Purified Polyclonal Ab antibody (antibody)

RRID:AB_2044647

This polyclonal antibody targets Mouse/Rat Contactin-2/TAG1 Affinity Purified Ab

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FOXP1 antibody [JC12] (antibody)

RRID:AB_1141518

This monoclonal antibody targets FOXP1 antibody [JC12]

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Monoclonal Anti-Myosin (Smooth) antibody produced in mouse (antibody)

RRID:AB_477239

This monoclonal antibody targets Myosin (Smooth) antibody produced in mouse

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Rabbit Anti-Islet 1, Neural Stem Cell Marker Polyclonal Antibody, Unconjugated (antibody)

RRID:AB_881306

This polyclonal antibody targets Islet 1 - Neural Stem Cell Marker

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Human Pax2 Affinity Purified Polyclonal Ab antibody (antibody)

RRID:AB_10889828

This unknown targets Human Pax2 Affinity Purified Ab

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Rabbit Anti-Mouse Collagen Type IV Polyclonal Antibody, Unconjugated (antibody)

RRID:AB_10576569

This polyclonal antibody targets Rabbit Mouse Collagen Type IV

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ALCAM (F84.1) antibody (antibody)

RRID:AB_831079

This monoclonal antibody targets ALCAM (F84.1)

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Ki67 antibody - Proliferation Marker (antibody)

RRID:AB_443209

This polyclonal antibody targets Ki67 antibody - Proliferation Marker

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Purified anti-Tubulin ? 3 (TUBB3) antibody (antibody)

RRID:AB_2313773

This monoclonal antibody targets Tubulin beta 3 (TUBB3)

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Sox-2 (Y-17) Antibody (antibody)

RRID:AB_2286684

This polyclonal antibody targets SOX2

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Anti-Sox9 antibody (antibody)

RRID:AB_2239761

This polyclonal antibody targets Sox9

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FOXP2 antibody (antibody)

RRID:AB_2107107

This polyclonal antibody targets Foxp2

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SATB2 antibody [SATBA4B10] (antibody)

RRID:AB_882455

This monoclonal antibody targets SATB2 antibody [SATBA4B10]

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Donkey anti-Mouse IgG (H+L) Highly Cross-Adsorbed Secondary Antibody, Alexa Fluor 568 (antibody)

RRID:AB_2534013

This polyclonal antibody targets Mouse IgG (H+L) Highly Cross-Adsorbed

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Ctip2 antibody [25B6] - ChIP Grade (antibody)

RRID:AB_2064130

This monoclonal antibody targets Bcl11b

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Anti-BARHL1 antibody produced in rabbit (antibody)

RRID:AB_1078266

This polyclonal antibody targets BARHL1 antibody produced in rabbit

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Lmx1b antibody (antibody)

RRID:AB_2314752

This unknown targets

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PLVAP antibody [174/2] (antibody)

RRID:AB_1658370

This monoclonal antibody targets Human PLVAP

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TBR1 antibody (antibody)

RRID:AB_2200219

This polyclonal antibody targets Tbr1

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D2-40 Lymphatic Endothelial Marker Monoclonal Antibody, Purified (antibody)

RRID:AB_2565182

This monoclonal antibody targets D2-40 Lymphatic Endothelial Marker

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Donkey anti-Mouse IgG (H+L) Highly Cross-Adsorbed Secondary Antibody, Alexa Fluor 488 (antibody)

RRID:AB_141607

This polyclonal antibody targets Mouse IgG (H+L) Highly Cross-Adsorbed

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Sox-10 (N-20) antibody (antibody)

RRID:AB_2195374

This polyclonal antibody targets Raised against peptide mapping to N-terminus of sox-10 of human origin

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Doublecortin (C-18) antibody (antibody)

RRID:AB_2088494

This polyclonal antibody targets Doublecortin (C-18)

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Anti-Tyrosine Hydroxylase Antibody (antibody)

RRID:AB_390204

This polyclonal antibody targets Tyrosine Hydroxylase

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Phox2b antibody (antibody)

RRID:AB_2315160

This unknown targets

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Anti-Choline Acetyltransferase antibody (antibody)

RRID:AB_2079751

This polyclonal antibody targets ChAT

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myogenin antibody (antibody)

RRID:AB_2146602

This monoclonal antibody targets Myog

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Donkey Anti-Goat IgG H&L (Alexa Fluor 647) antibody (antibody)

RRID:AB_2687955

This polyclonal antibody targets Goat IgG H&L

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Anti-SOX2 antibody (antibody)

RRID:AB_2341193

This polyclonal antibody targets sox2

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Anti-Peripherin antibody (antibody)

RRID:AB_90725

This polyclonal antibody targets Peripherin

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Pax6 antibody (antibody)

RRID:AB_2315065

This unknown targets

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Monoclonal anti Parvalbumin antibody (antibody)

RRID:AB_10000343

This monoclonal antibody targets parvalbumin

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Alexa Fluor antibody (antibody)

RRID:AB_2340862

This polyclonal antibody targets Mouse IgG (H+L)

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anti-mouse Tlx3 polyclonal antibody (antibody)

RRID:AB_2532145

This polyclonal antibody targets Tlx3

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FOXP2 (N-16) antibody (antibody)

RRID:AB_2107124

This polyclonal antibody targets FOXP2

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SIX2 antibody (antibody)

RRID:AB_2189084

This polyclonal antibody targets SIX2

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ImageJ (tool)

RRID:SCR_003070

Software tool as an open source Java-based image processing program designed for scientific multidimensional images. ImageJ has been transformed to ImageJ2 application to improve data engine to be sufficient to analyze modern datasets.

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Imaris (tool)

RRID:SCR_007370

Interactive Vision In The Life SciencesCombining speed, precision and ease-of-use, Imaris provides an impressive range of capabilities for working with three-dimensional images. Move easily between simple and advanced 3D views. Use flexible editing and processing functions, such as interactive surface rendering and object slicing capabilities. And output to standard TIFF, Quicktime and AVI formats. Imaris accepts virtually all image formats that are used in confocal microscopy and many of those used in wide-field image acquisition.BitPlane, Inc. also releases the following companion products:- ImarisXT is a multi-functional two-way interface from Imaris to both classic programming languages and to Matlab.- Imaris MeasurementPro and Imaris Track provide the ability to segment and follow the movement of independent objects in a 3D image over time. Objects can either be Surface Objects or Spots, created automatically or manually.- ImarisColoc enables users to easily isolate, visualize, and quantify regional overlap in 3D and 4D images and automates the process of selecting colocalized image areas.

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