The McGlinn Group is focused on elucidating novel gene networks that drive growth and identity in the early embryo.

Research

The McGlinn Group is particularly interested in critical developmental regulators, the Hox genes, and how microRNAs shape Hox functional output during formation of the vertebral column and spinal cord.

They use elegant mouse genetics coupled with cutting edge functional genomics technologies to unravel novel gene networks and mechanisms of regulation.

McGlinn members group photo
  • microRNA control of Hox gene networks
  • Genomic/epigenomic regulation of axis elongation and vertebral patterning
  • Formation and patterning of spinal cord circuitry
  • Evolutionary acquisition of microRNAs shapes developmental networks

Developmental gene networks

The accuracy and reproducibility with which the vertebrate embryo develops is remarkable. Our lab investigates how developmental gene networks are regulated, both at a transcriptional and post-transcriptional level, to achieve such exquisite reproducibility. 

Our lab continues to make seminal contributions to the understanding of how microRNA regulatory mechanisms contribute to refining or stabilising Hox functional output in mouse, how this relates to human disease and how differences in microRNA acquisition between species may shape differences in morphology.

In particular, we are interested in how the developmental modules that define total vertebral number are integrated with those that impart vertebral identity. Moreover, our lab has developed novel genetic tools to address critical questions regarding formation and function of neurons within the spinal cord that relay sensory information directly to the brain. 

Fluorescent transgenic reporter in mouse reveals dynamic Hox gene expression boundaries
Expression of miR-10 in the developing snake, Ophiophagus Hannah.
Neural networks of the spinal cord

 

Authors
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Jansz N, Keniry A, Trussart M, Bildsoe H, Beck T, Tonks ID, Mould AW, Hickey P, Breslin K, Iminitoff M, Ritchie ME, McGlinn E, Kay GF, Murphy JM, Blewitt ME.

Smchd1 regulates long-range chromatin interactions on the inactive X chromosome and at Hox clusters.

Nat Struct Mol Biol. 2018 Aug 20. doi: 10.1038/s41594-018-0111-z. 

Meyer SE, Muench DE, Rogers AM, Newkold TJ, Orr E, O'Brien E, Perentesis JP, Doench JG, Lal A, Morris PJ, Thomas CJ, Lieberman J, McGlinn E, Aronow BJ, Salomonis N, Grimes HL.

miR-196b target screen reveals mechanisms maintaining leukemia stemness with therapeutic potential.

J Exp Med. 2018 Aug 6;215(8):2115-2136. doi: 10.1084/jem.20171312. Epub 2018 Jul 11.

Pearson HB, McGlinn E, Phesse TJ, Schlüter H, Srikumar A, Gödde NJ, Woelwer CB, Ryan A, Phillips WA, Ernst M, Kaur P, Humbert P.

The polarity protein Scrib mediates epidermal development and exerts a tumor suppressive function during skin carcinogenesis.

Mol Cancer. 2015 Sep 17;14:169. doi: 10.1186/s12943-015-0440-z.

Wong SF, Agarwal V, Mansfield JH, Denans N, Schwartz MG, Prosser HM, Pourquié O, Bartel DP, Tabin CJ, McGlinn E.

Independent regulation of vertebral number and vertebral identity by microRNA-196 paralogs.

Proc Natl Acad Sci U S A. 2015 Sep 1;112(35):E4884-93. doi: 10.1073/pnas.1512655112. Epub 2015 Aug 17.

Vonk FJ, Casewell NR, Henkel CV, Heimberg AM, Jansen HJ, McCleary RJ, Kerkkamp HM, Vos RA, Guerreiro I, Calvete JJ, Wüster W, Woods AE, Logan JM, Harrison RA, Castoe TA, de Koning AP, Pollock DD, Yandell M, Calderon D, Renjifo C, Currier RB, Salgado D, Pla D, Sanz L, Hyder AS, Ribeiro JM, Arntzen JW, van den Thillart GE, Boetzer M, Pirovano W, Dirks RP, Spaink HP, Duboule D, McGlinn E, Kini RM, Richardson MK.

The king cobra genome reveals dynamic gene evolution and adaptation in the snake venom system.

PNAS 2013;110(51):20651-6. doi: 10.1073/pnas.1314702110.

Allen JM, McGlinn E, Hill A, Warman ML.

Autopodial development is selectively impaired by misexpression of chordin-like 1 in the chick limb.

Dev Biol. 2013 Sep 1;381(1):159-69. doi: 10.1016/j.ydbio.2013.06.003. Epub 2013 Jun 10.

Hu JK, McGlinn E, Harfe BD, Kardon G, Tabin CJ.

Autonomous and nonautonomous roles of Hedgehog signaling in regulating limb muscle formation.

Genes Dev. 2012 Sep 15;26(18):2088-102. doi: 10.1101/gad.187385.112.

Heimberg A, McGlinn E.

Building a robust a-p axis.

Curr Genomics. 2012 Jun;13(4):278-88. doi: 10.2174/138920212800793348.

Town L, McGlinn E, Davidson TL, Browne CM, Chawengsaksophak K, Koopman P, Richman JM, Wicking C.

Tmem26 is dynamically expressed during palate and limb development but is not required for embryonic survival.

PLoS One. 2011;6(9):e25228. doi: 10.1371/journal.pone.0025228. Epub 2011 Sep 29.

Haramati S, Chapnik E, Sztainberg Y, Eilam R, Zwang R, Gershoni N, McGlinn E, Heiser PW, Wills AM, Wirguin I, Rubin LL, Misawa H, Tabin CJ, Brown R Jr, Chen A, Hornstein E.

miRNA malfunction causes spinal motor neuron disease.

PNAS 2010 Jul 20;107(29):13111-6. doi: 10.1073/pnas.1006151107. Epub 2010 Jun 29.

Bruce SJ, Butterfield NC, Metzis V, Town L, McGlinn E and Wicking CA.

Inactivation of patched1 in the mouse limb has novel inhibitory effects on the chondrogenic programme.

J Biol Chem. 2010 Sep 3;285(36):27967–27981. doi: 10.1074/jbc.M109.091785. Epub 2010 Jun 24.

McGlinn E, Yekta S, Mansfield JH, Soutschek J, Bartel DP, Tabin CJ.

In ovo application of antagomiRs indicates a role for miR-196 in patterning the chick axial skeleton through Hox gene regulation.

Proc Natl Acad Sci U S A. 2009 Nov 3;106(44):18610-5. doi: 10.1073/pnas.0910374106. Epub 2009 Oct 21.

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.

Dev Dyn. 2009 Dec;238(12):3175-84. doi: 10.1002/dvdy.22126.

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 Oct;136(20):3515-24. doi: 10.1242/dev.037507.

Mao J, McGlinn E, Huang P, Tabin CJ, McMahon AP.

Fgf-dependent Etv4/5 activity is required for posterior restriction of Sonic Hedgehog and promoting outgrowth of the vertebrate limb.

Dev Cell. 2009 Apr;16(4):600-6. doi: 10.1016/j.devcel.2009.02.005.

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.

Dev Dyn. 2008 Apr;237(4):1172-82. doi: 10.1002/dvdy.21508.

Scherz P, McGlinn E, Nissim S and Tabin CJ.

Extended exposure to Sonic hedgehog is required for patterning the posterior digits of the vertebrate limb.

Dev Biol. 2007 Aug 15; 308(2): 343–354. doi: 10.1016/j.ydbio.2007.05.030. Epub 2007 May 31.

McGlinn E, van Bueren KL, Fiorenza S, Mo R, Poh AM, Forrest A, Soares MB, Bonaldo Mde F, Grimmond S, Hui CC, Wainwright B, Wicking C.

Pax9 and Jagged1 act downstream of Gli3 in vertebrate limb development.

Mech Dev. 2005 Nov;122(11):1218-33. Epub 2005 Aug 1.

Hewitt C, Wilson P, McGlinn E, MacFarlane G, Papageorgiou A, Woodwards RT, Sloan P, Gollin SM, Paterson I, Parkinson KK, Read AP, Thakker N.

DLC1 is unlikely to be a primary target for deletions on chromosome arm 8p22 in head and neck squamous cell carcinoma.

Cancer Lett. 2004 Jun 25;209(2):207-13.

Hall MA, McGlinn E, Coakley G, Fisher SA, Boki K, Middleton D, Kaklamani E, Moutsopoulos H, Loughran TP Jr, Ollier WE, Panayi GS, Lanchbury JS.

Genetic polymorphism of IL-12 p40 gene in immune-mediated disease.

Genes Immun. 2000 Feb;1(3):219-24.

Wilson PJ, McGlinn E, Marsh A, Evans T, Arnold J, Wright K, Biden K, Young J, Wainwright B, Wicking C, Chenevix-Trench G.

Sequence variants of DLC1 in colorectal and ovarian tumours.

Hum Mutat. 2000;15(2):156-65.

Thomas GR, Costelloe EA, Lunn DP, Stacey KJ, Delaney SJ, Passey R, McGlinn EC, McMorran BJ, Ahadizadeh A, Geczy CL, Wainwright BJ, Hume DA.

G551D cystic fibrosis mice exhibit abnormal regulation of inflammation in lungs and macrophages.

J Immunol. 2000 Apr 1;164(7):3870-7.

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Edwina McGlinn

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