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Licia Selleri M.D., Ph.D.

Genetic and regulatory control of craniofacial morphogenesis in embryonic development, evolution, and disease

Licia Selleri M.D., Ph.D.

The laboratory studies the genetic and regulatory basis of how elaborately patterned tissues form during embryonic development and evolution. The laboratory combines different genetic approaches, using the mouse as a model, to understand the mechanisms underpinning basic developmental processes related to cranial and appendicular morphogenesis. They discovered that homeodomain-containing transcription factors of the Pbx family, also known as Hox-cofactors, are critical developmental regulators through the transcriptional control of target genes within tissue-specific regulatory networks. They use genetically-engineered and ethylnitrosourea (ENU)-mutagenized mouse lines and recently utilize additional animal models such as jerboas and primates. The ultimate goal of the laboratory is to identify novel genes and regulatory networks underlying morphogenesis of craniofacial structures, morphological variation, evolution, and human craniofacial congenital disease.

Select Publications:

Hox and Pbx Factors Control Retinoic Acid Synthesis during Hindbrain      Segmentation. A. Vitobello*, E. Ferretti*, X. Lampe, S. Dulcre’, M. Ori, L. Selleri# & F. Rilji#. (*Joint co-first authors)    (#Joint co-corresponding authors) Developmental Cell 20(4):469-82, 2011

A Conserved Pbx-Wnt-p63-Irf6 Regulatory Module Controls Face Morphogenesis by Promoting Epithelial Apoptosis. E. Ferretti, B. Li, R. Zewdu, V. Wells, J. Hebert, T. Carroll, M. Dixon, M. Depew,   and L. SelleriDevelopmental Cell 21(4):627-41, 2011.  Highlighted in ‘Science Editor’s Choice’ - Science issue of October 28, 2011: http://www.sciencemag.org/content/334/6055/twil.full - compilation-1-2-article-title-1  Highlighted in the ‘Faculty of 1000’; Highlighted in ‘Medical News Today’;  Highlighted in ‘BioTechniques’ .  

Congenital Asplenia in Mice and Humans with Mutations in a Pbx/Nkx2-5/p15  Module. M. Koss, A. Bolze, A. Brendolan, M. Saggese, T. Capellini, K. Eboljova, B. Boisson, O.     Prall, D. Elliott, M. Solloway, C.P. Chang, C. Hidaka, R. Harvey, JL Casanova, and L. Selleri.  Developmental Cell 22(5):913-26, 2012

Ribosomal protein SA haplo-insufficiency in humans with isolated congenital asplenia. A. Bolze, N. Mahlaoui, B. Turner, N. Trede, S. R. Ellis, A. Abhyankar, Y. Itan, S.    Brebner, P. Sackstein, A. Puel, C. Picard, L. Abel, S. N. Faust, A. P. Williams, R. Baretto, M. Duddridge, U. Kini, A. Pollard, C. Gaud, P. Frange, D. Orbach, JF. Emile,     JL Stephan, R. Sorensen, L. Hammarstrom, M. E. Conley, L. Selleri and JL.  Casanova. Science 340(6135):976-8, 2013

ESCRTII-Vps25 constrains digit number by endosome-mediated selective modulation of FGF-   SHH signaling. K. Handschuh, J. Fenstra, M. Koss, E. Ferretti, M. Risolino, R. Zewdu, PX Peng, H. Alcorn, M. Depew, R. Rivi, J. Manak, K.V. Anderson, E. Lacy, and L. Selleri. Cell Reports 9(2):674-87, 2014.  Highlighted in ‘Science Editor’s Choice’ - Science issue of October 17, 2014:             http://www.sciencemag.org/content/346/6207/311.2.short. Highlighted in NICHD Spotlights – ‘It’s in the DNA: Animal Models Offer Clues to Human Development - Mouse study reveals potential clue to extra fingers or toes’: http://www.nichd.nih.gov/news/releases/Pages/112114-polydactyly.aspx

A comparative encyclopedia of DNA elements in the mouse genome. F. Yue et al. Mouse ENCODE Consortium (L. Selleri is a co-author among 137 authors). Nature 515(7527):355-64, 2014

Principles of regulatory information conservation between mouse and human. Y. Cheng  et al.  Mouse ENCODE Consortium (L. Selleri is a co-author among 134 authors).    Nature 515(7527):371-5, 2014

Mouse regulatory DNA landscapes reveal global principles of cis-regulatory evolution. J. Vierstra, Rynes E, Sandstrom R, Zhang M, Canfield T, Hansen RS, Stehling-Sun S,     Sabo PJ, Byron R, Humbert R, Thurman RE, Johnson AK, Vong S, Lee K, Bates D, Neri F, Diegel M, Giste E, Haugen E, Dunn D, Wilken MS,     Josefowicz S, Samstein R, Chang KH, Eichler EE, De Bruijn M, Reh TA, Skoultchi A, Rudensky A, Orkin SH, Papayannopoulou T, Treuting PM, Selleri L, Kaul R, Groudine M, Bender MA, Stamatoyannopoulos JA.            Science 346(6212):1007-12, 2014

Enhancer divergence and cis-regulatory evolution in the human and chimpanzee neural crest.  S. Prescott, R. Srinivasan, I. Narvaiza, C.Marchetto, I. Grishina, L. Selleri, F.H. Gage, T. Swigut, and J. Wysocka.  Cell 163(1):68-83, 2011.  Highlighted in the ‘Faculty of 1000’; Comment on: Nat Rev Genet. 2015     Nov;16(11):625.  “Evolution: Regulatory evolution of human craniofacial morphology” by J. Osório; Comment on: Cell. 2015 Sep 24;163(1):24-6. “Coordinating the human  looks” by V. Haberle, and A. Stark.

F. Brinkley, S. Fisher, M.P. Harris, G.P. Holmes, J.E. Hooper, E.W. Jabs, K.L. Jones, C. Kesselman, O.D. Klein, R.L. Maas, M.L. Marazita, L. Selleri, R.A.     Spritz, H. van Bakel,   A. Visel, T.J. Williams, J. Wysocka, The FaceBase Consortium and Y. Chai.  The FaceBase Consortium: A Comprehensive Resource for Craniofacial Researchers. Development 2016 Jun 10. pii: dev.135434. [Epub ahead of print]