Papers

PREPRINTS

Semprich CI, Metzis V, Patel H, Briscoe J, Storey KG (2019). ERK1/2 signalling dynamics promote neural differentiation by regulating the polycomb repressive complex. bioRxiv 2019;586719.
doi: https://doi.org/10.1101/586719

In this work we demonstrate the chromatin dynamics and changes in polycomb occupancy that occur at neural genes as cells progress to a spinal cord fate.


Exelby K, Herrera-Delgado E, Garcia Perez L, Perez-Carrasco R, Sagner A, Metzis V, Sollich P, Briscoe J. Precision of Tissue Patterning is Controlled by Dynamical Properties of Gene Regulatory Networks. bioRxiv 2019;721043. doi:https://doi.org/10.1101/721043

In this work we demonstrate the impact of regulatory element usage in promoting precise tissue patterns in the neural tube.


PEER-REVIEWED PUBLICATIONS

RESEARCH ARTICLE

Metzis V, Steinhauser S, Pakanavicius E, Gouti M, Stamataki D, Ivanovitch K, Watson T, Rayon T, Mousavy Gharavy SN, Lovell-Badge R, Luscombe NM, Briscoe J. Nervous System Regionalization Entails Axial Allocation before Neural Differentiation. Cell. 2018;175(4):1105- 1118.e17. doi:10.1016/j.cell.2018.09.040

Preprint available at doi:10.1101/229203

PMCID: PMC6218657

This work provides evidence that the competence to form spinal cord during development is transient, and determined by chromatin remodelling events that take place in cells before they form neural progenitors. The data demonstrate that cells acquire regional identity prior to neural identity, prompting revisions to previous models of neural induction.

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– Simon CS, Hadjantonakis AK. Top to Tail: Anterior- Posterior Patterning Precedes Regional Nervous System Identity. Cell. 2018;175(4):905-907.

Press Release

Crick news


RESEARCH ARTICLE

Gabrysova L, Alvarez-Martinez M, Luisier R, Cox LS, Sodenkamp J, Hosking C, Perez-Mazliah D, Whicher C, Kannan Y, Potempa K, Wu X, Bhaw L, Wende H, Sieweke MH, Elgar G, Wilson M, Briscoe J, Metzis V, et al. c-Maf controls immune responses by regulating disease-specific gene networks and repressing IL-2 in CD4(+) T cells. Nat Immunol. 2018;19(5):497-507.

PMCID: PMC5988041

This work highlights the importance of c-Maf in regulating cytokine gene expression in vivo. By defining the transcriptional targets and chromatin landscape in T cells, these data reveal how context-specific immune responses are elicited by c-Maf under different pathologies.

Press Release

Crick news


RESEARCH ARTICLE

Lu H, Galeano MCR, Ott E, Kaeslin G, Kausalya PJ, Kramer C, Ortiz-Bruchle N, Hilger N, Metzis V, Hiersche M, et al. Mutations in DZIP1L, which encodes a ciliary-transition-zone protein, cause autosomal recessive polycystic kidney disease. Nat Genet. 2017;49(7):1025-1034

PMCID: PMC5687889

This work identified DZIP1L as a novel gene causing autosomal recessive polycystic kidney disease. We developed mechanistic insight into the disease using human patient fibroblast and both mouse and fish models that recapitulate the disease, revealing the role of DZIP1L in regulating the trafficking of proteins through the transition zone of the primary cilium.


ADVANCED REVIEW

Cortes CR, Metzis V, Wicking C. Unmasking the ciliopathies: craniofacial defects and the primary cilium. Wiley Interdiscip Rev Dev Biol. 2015;4(6):637-53.

In this review, we discuss a major class of congenital defects known as ciliopathies. We highlight the prevalence of craniofacial defects associated with these heterogeneous disorders, and discuss the underlying mechanisms.


REVIEW

Gouti M, Metzis V, Briscoe J. The route to spinal cord cell types: a tale of signals and switches. Trends Genet. 2015;31(6):282-9.

PMID: 25823696

In this review, we focus on the cell fate decisions and signals that promote spinal cord development, highlighting the role of neuromesodermal progenitors that form the posterior part of the embryo.


RESEARCH ARTICLE

Metzis V, Courtney AD, Kerr MC, Ferguson C, Rondon Galeano MC, Parton RG, Wainwright BJ, Wicking C. Patched1 is required in neural crest cells for the prevention of orofacial clefts. Human Molecular Genetics. 2013;22:5026-5035

PMID: 23900075

This work demonstrated the role of Hedgehog signalling in the genesis of cleft lip in vivo. We revealed the genetic interactions in neural crest cells and morphogenic processes captured with confocal video microscopy, that direct upper lip morphogenesis in mouse embryos.


RESEARCH ARTICLE

Bruce SJ, Butterfield NC, Metzis V, Town L, McGlinn E, Wicking C. Inactivation of Patched1 in the mouse limb has novel inhibitory effects on the chondrogenic program. The Journal of Biological Chemistry. 2010;285:27967-27981

PMCID: PMC2934663

Using an in vitro system to model limb cartilage development, we demonstrate a novel role for Ptch1 in the maintenance of cell integrity during the early phases of cartilage condensation.


RESEARCH ARTICLE

Butterfield NC, Metzis V, McGlinn E, Bruce SJ, Wainwright BJ, Wicking C. Patched 1 is a crucial determinant of asymmetry and digit number in the vertebrate limb. Development. 2009;136: 3515-3524

PMID: 19783740

This work revealed the genetic network downstream of Ptch1 responsible for controlling digit number and asymmetry in the mouse limb.


RESEARCH ARTICLE

Town L, McGlinn E, Fiorenza S, Metzis V, Butterfield NC, Richman JM, Wicking C. The metalloendopeptidase gene Pitrm1 is regulated by hedgehog signaling in the developing mouse limb and is expressed in muscle progenitors. Developmental Dynamics. 2009;238: 3175-3184

PMID: 19877269

We provide the first characterisation of the expression of Pitrm1, a novel gene regulated by Hedgehog signalling, during embryonic development.


RESEARCH ARTICLE

McGlinn E, Richman JM, Metzis V, Town L, Butterfield NC, Wainwright BJ, Wicking C. Expression of the NET family member Zfp503 is regulated by hedgehog and BMP signaling in the limb. Developmental Dynamics. 2008;237: 1172-1182

PMID: 18351672

We document the in vivo expression pattern of Zfp503 in chick and mouse embryos, and show that its strict spatio-temporal pattern in the limb bud is dependent on both Hedgehog and BMP signalling.


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