S. A. Brown, Holoprosencephaly due to mutations in ZIC2, a homologue of Drosophila odd-paired, Nat Genet, vol.20, pp.180-183, 1998.

B. D. Solomon, Mutations in ZIC2 in human holoprosencephaly: description of a novel ZIC2 specific phenotype and comprehensive analysis of 157 individuals, J Med Genet, vol.47, pp.513-524, 2010.
URL : https://hal.archives-ouvertes.fr/inserm-00439659

S. Mercier, New findings for phenotype-genotype correlations in a large European series of holoprosencephaly cases, J Med Genet, vol.48, pp.752-760, 2011.
URL : https://hal.archives-ouvertes.fr/inserm-00626407

N. Warr, Zic2-associated holoprosencephaly is caused by a transient defect in the organizer region during gastrulation, Hum Mol Genet, vol.17, pp.2986-2996, 2008.

T. Nagai, Zic2 regulates the kinetics of neurulation, Proc Natl Acad Sci, vol.97, pp.1618-1623, 2000.

P. Elms, Overlapping and distinct expression domains of Zic2 and Zic3 during mouse gastrulation, Gene Expr Patterns, vol.4, pp.505-511, 2004.

F. L. Conlon, A primary requirement for nodal in the formation and maintenance of the primitive streak in the mouse, Development, vol.120, pp.1919-1928, 1994.

R. Houtmeyers, Zic2 mutation causes holoprosencephaly via disruption of NODAL signalling, Hum Mol Genet, 2016.

D. P. Norris and . Cilia, calcium and the basis of left-right asymmetry, BMC Biol, vol.10, 2012.

S. Nonaka, H. Shiratori, Y. Saijoh, and H. Hamada, Determination of left-right patterning of the mouse embryo by artificial nodal flow, Nature, vol.418, pp.96-99, 2002.

J. Collignon, I. Varlet, and E. J. Robertson, Relationship between asymmetric nodal expression and the direction of embryonic turning, Nature, vol.381, pp.155-158, 1996.

L. A. Lowe, Conserved left-right asymmetry of nodal expression and alterations in murine situs inversus, Nature, vol.381, pp.158-161, 1996.

, SCIEnTIFIC REPORtS |, vol.8, 2018.

J. Brennan, D. P. Norris, and E. J. Robertson, Nodal activity in the node governs left-right asymmetry, Genes Dev, vol.16, pp.2339-2344, 2002.

Y. Saijoh, Distinct transcriptional regulatory mechanisms underlie left-right asymmetric expression of lefty-1 and lefty-2, Genes Dev, vol.13, pp.259-269, 1999.

G. Ammirabile, Pitx2 confers left morphological, molecular, and functional identity to the sinus venosus myocardium, Cardiovasc Res, vol.93, pp.291-301, 2012.

C. M. Chen, D. Norris, and S. Bhattacharya, Transcriptional control of left-right patterning in cardiac development, Pediatr Cardiol, vol.31, pp.371-377, 2010.

I. M. Dykes, Left Right Patterning, Evolution and Cardiac Development, J. Cardiovasc. Dev. Dis, vol.1, pp.52-72, 2014.

A. F. Ramsdell, Left-right asymmetry and congenital cardiac defects: getting to the heart of the matter in vertebrate left-right axis determination, Dev Biol, vol.288, pp.1-20, 2005.

T. Nakamura and H. Hamada, Left-right patterning: conserved and divergent mechanisms, Development, vol.139, pp.3257-3262, 2012.

H. Shiratori and H. Hamada, The left-right axis in the mouse: from origin to morphology, Development, vol.133, pp.2095-2104, 2006.

M. Campione and D. Franco, Current Perspectives in CardiacLaterality, J Cardiovasc Dev Dis, vol.3, 2016.

M. J. Sutherland and S. M. Ware, Disorders of left-right asymmetry: heterotaxy and situs inversus, Am J Med Genet C Semin Med Genet, vol.151, pp.307-317, 2009.

B. Mohapatra, Identification and functional characterization of NODAL rare variants in heterotaxy and isolated cardiovascular malformations, Hum Mol Genet, vol.18, pp.861-871, 2009.

K. S. Barratt, H. C. Glanville-jones, and R. M. Arkell, The Zic2 gene directs the formation and function of node cilia to control cardiac situs, Genesis, vol.52, pp.626-635, 2014.

M. Campione, Pitx2 expression defines a left cardiac lineage of cells: evidence for atrial and ventricular molecular isomerism in the iv/iv mice, Dev Biol, vol.231, pp.252-264, 2001.

K. Matsuda, ChIP-seq analysis of genomic binding regions of five major transcription factors in mouse epiblast stem cells that highlights a central role for ZIC2, 2017.

Z. Luo, Zic2 is an enhancer-binding factor required for embryonic stem cell specification, Mol Cell, vol.57, pp.685-694, 2015.

Y. Kojima, The transcriptional and functional properties of mouse epiblast stem cells resemble the anterior primitive streak, Cell Stem Cell, vol.14, pp.107-120, 2014.

C. Buecker, Reorganization of enhancer patterns in transition from naive to primed pluripotency, Cell Stem Cell, vol.14, pp.838-853, 2014.

G. Hu and P. A. Wade, NuRD and pluripotency: a complex balancing act, Cell Stem Cell, vol.10, pp.497-503, 2012.

B. Davies, Site specific mutation of the Zic2 locus by microinjection of TALEN mRNA in mouse CD1, C3H and C57BL/6J oocytes, PLoS One, vol.8, 2013.

S. D. Bamforth, Cited2 controls left-right patterning and heart development through a Nodal-Pitx2c pathway, Nat Genet, vol.36, pp.1189-1196, 2004.

P. Scambler, 22q11 deletion syndrome: a role for TBX1 in pharyngeal and cardiovascular development, Pediatric cardiology, vol.31, pp.378-390, 2010.

I. M. Dykes, HIC2 is a novel dosage-dependent regulator of cardiac development located within the distal 22q11 deletion syndrome region, Circ Res, vol.115, pp.23-31, 2014.

D. Szumska, VACTERL/caudal regression/Currarino syndrome-like malformations in mice with mutation in the proprotein convertase Pcsk5, Genes Dev, vol.22, pp.1465-1477, 2008.

J. E. Schneider, Identification of cardiac malformations in mice lacking Ptdsr using a novel high-throughput magnetic resonance imaging technique, BMC Dev Biol, vol.4, 2004.

P. Elms, P. Siggers, D. Napper, A. Greenfield, and R. Arkell, Zic2 is required for neural crest formation and hindbrain patterning during mouse development, Dev Biol, vol.264, pp.391-406, 2003.

J. W. Seo, N. A. Brown, S. Y. Ho, and R. H. Anderson, Abnormal laterality and congenital cardiac anomalies. Relations of visceral and cardiac morphologies in the iv/iv mouse, Circulation, vol.86, pp.642-650, 1992.

V. Hildreth, Left cardiac isomerism in the Sonic hedgehog null mouse, J Anat, vol.214, pp.894-904, 2009.

C. Meno, lefty-1 is required for left-right determination as a regulator of lefty-2 and nodal, Cell, vol.94, pp.287-297, 1998.

Y. T. Yan, Conserved requirement for EGF-CFC genes in vertebrate left-right axis formation, Genes Dev, vol.13, pp.2527-2537, 1999.

U. Bartram, J. Wirbelauer, and C. P. Speer, Heterotaxy syndrome-asplenia and polysplenia as indicators of visceral malposition and complex congenital heart disease, Biol Neonate, vol.88, pp.278-290, 2005.

S. P. Oh and E. Li, The signaling pathway mediated by the type IIB activin receptor controls axial patterning and lateral asymmetry in the mouse, Genes Dev, vol.11, pp.1812-1826, 1997.

V. Duboc, E. Rottinger, F. Lapraz, L. Besnardeau, and T. Lepage, Left-right asymmetry in the sea urchin embryo is regulated by nodal signaling on the right side, Dev Cell, vol.9, pp.147-158, 2005.

A. K. Ryan, Pitx2 determines left-right asymmetry of internal organs in vertebrates, Nature, vol.394, pp.545-551, 1998.

A. Kawasumi, Left-right asymmetry in the level of active Nodal protein produced in the node is translated into left-right asymmetry in the lateral plate of mouse embryos, Dev Biol, vol.353, pp.321-330, 2011.

D. P. Norris, J. Brennan, E. K. Bikoff, and E. J. Robertson, The Foxh1-dependent autoregulatory enhancer controls the level of Nodal signals in the mouse embryo, Development, vol.129, pp.3455-3468, 2002.

H. Adachi, Determination of left/right asymmetric expression of nodal by a left side-specific enhancer with sequence similarity to a lefty-2 enhancer, Genes Dev, vol.13, pp.1589-1600, 1999.

C. Papanayotou, A novel nodal enhancer dependent on pluripotency factors and smad2/3 signaling conditions a regulatory switch during epiblast maturation, PLoS Biol, vol.12, 2014.
URL : https://hal.archives-ouvertes.fr/hal-01060190

S. D. Vincent, N. R. Dunn, S. Hayashi, D. P. Norris, and E. J. Robertson, Cell fate decisions within the mouse organizer are governed by graded Nodal signals, Genes Dev, vol.17, pp.1646-1662, 2003.
DOI : 10.1101/gad.1100503

URL : https://hal.archives-ouvertes.fr/hal-02130359

D. P. Norris and E. J. Robertson, Asymmetric and node-specific nodal expression patterns are controlled by two distinct cis-acting regulatory elements, Genes Dev, vol.13, pp.1575-1588, 1999.
DOI : 10.1101/gad.13.12.1575

URL : http://genesdev.cshlp.org/content/13/12/1575.full.pdf

S. M. Purandare, A complex syndrome of left-right axis, central nervous system and axial skeleton defects in Zic3 mutant mice, Development, vol.129, pp.2293-2302, 2002.

Z. Jiang, Zic3 is required in the extra-cardiac perinodal region of the lateral plate mesoderm for left-right patterning and heart development, Hum Mol Genet, vol.22, pp.879-889, 2013.

S. M. Ware, K. G. Harutyunyan, and J. W. Belmont, Heart defects in X-linked heterotaxy: evidence for a genetic interaction of Zic3 with the nodal signaling pathway, Dev Dyn, vol.235, pp.1631-1637, 2006.

, SCIEnTIFIC REPORtS |, vol.8, 2018.

L. Brown, M. Paraso, R. Arkell, and S. Brown, In vitro analysis of partial loss-of-function ZIC2 mutations in holoprosencephaly: alanine tract expansion modulates DNA binding and transactivation, Hum Mol Genet, vol.14, pp.411-420, 2005.

L. A. Lowe, S. Yamada, and M. R. Kuehn, Genetic dissection of nodal function in patterning the mouse embryo, Development, vol.128, pp.1831-1843, 2001.

A. Beckers, L. Alten, C. Viebahn, P. Andre, and A. Gossler, The mouse homeobox gene Noto regulates node morphogenesis, notochordal ciliogenesis, and left right patterning, Proc Natl Acad Sci, vol.104, pp.15765-15770, 2007.
DOI : 10.1073/pnas.0704344104

URL : https://www.pnas.org/content/pnas/104/40/15765.full.pdf

Y. Saijoh, S. Oki, S. Ohishi, and H. Hamada, Left-right patterning of the mouse lateral plate requires nodal produced in the node, Dev Biol, vol.256, pp.160-172, 2003.

H. Shiratori and H. Hamada, TGFbeta signaling in establishing left-right asymmetry, Semin Cell Dev Biol, vol.32, pp.80-84, 2014.
DOI : 10.1016/j.semcdb.2014.03.029

C. Tanaka, R. Sakuma, T. Nakamura, H. Hamada, and Y. Saijoh, Long-range action of Nodal requires interaction with GDF1, Genes Dev, vol.21, pp.3272-3282, 2007.
DOI : 10.1101/gad.1623907

URL : http://genesdev.cshlp.org/content/21/24/3272.full.pdf

K. Kitajima, S. Oki, Y. Ohkawa, T. Sumi, and C. Meno, Wnt signaling regulates left-right axis formation in the node of mouse embryos, Dev Biol, vol.380, pp.222-254, 2013.

S. Field, Pkd1l1 establishes left-right asymmetry and physically interacts with Pkd2, Development, vol.138, pp.1131-1142, 2011.
DOI : 10.1242/dev.058149

URL : http://dev.biologists.org/content/138/6/1131.full.pdf

A. Raya, Notch activity induces Nodal expression and mediates the establishment of left-right asymmetry in vertebrate embryos, Genes Dev, vol.17, pp.1213-1218, 2003.

J. Crocker, E. P. Noon, and D. L. Stern, The Soft Touch: Low-Affinity Transcription Factor Binding Sites in Development and Evolution, Curr Top Dev Biol, vol.117, pp.455-469, 2016.

J. Bentham, Maternal high-fat diet interacts with embryonic Cited2 genotype to reduce Pitx2c expression and enhance penetrance of left-right patterning defects, Hum Mol Genet, vol.19, pp.3394-3401, 2010.

J. E. Schneider, Rapid identification and 3D reconstruction of complex cardiac malformations in transgenic mouse embryos using fast gradient echo sequence magnetic resonance imaging, J Mol Cell Cardiol, vol.35, pp.217-222, 2003.

R. C. Gentleman, Bioconductor: open software development for computational biology and bioinformatics, Genome Biol, vol.5, 2004.

W. Huber, A. Von-heydebreck, H. Sultmann, A. Poustka, and M. Vingron, Variance stabilization applied to microarray data calibration and to the quantification of differential expression, Bioinformatics, vol.18, issue.1, pp.96-104, 2002.

G. K. Smyth, In Bioinformatics and Computational Biology Solutions using R and Bioconductor, vol.397, issue.420, 2005.

Y. Benjamini and Y. Hochberg, Controlling the False Discovery Rate-a Practical and Powerful Approach to Multiple Testing, Journal of the Royal Statistical Society Series B-Methodological, vol.57, pp.289-300, 1995.

I. Ulitsky, Expander: from expression microarrays to networks and functions, Nat Protoc, vol.5, pp.303-322, 2010.

K. M. Correia and R. A. Conlon, Whole-mount in situ hybridization to mouse embryos, Methods, vol.23, pp.335-338, 2001.

J. T. Robinson, Integrative genomics viewer, Nat Biotechnol, vol.29, pp.24-26, 2011.