Faculty

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Robert E Maxson, PhD
Professor of Biochemistry & Molecular Biology
Biochemistry and Molecular Biology
NOR 5334 1441 Eastlake Avenue Health Sciences Campus Los Angeles
+1 323 865 0633

Overview

The two broad interests of the Maxson laboratory are the molecular genetic basis of embryonic pattern formation and the identification and of genetic loci that influence cancer risk. In embryonic development, we focus on processes that regulate the development of the cranial neural crest, a popultion of multipotent cells that originate in the neural tube and migrate to distant sites, where they differentiate into a variety of cell types, including bone muscle, nerve, and cartilage. We are particuarly interested in genetic factors that control the multipotency of cranial neural crest. We are also interested in the formation and function of tissue boundaries between neural crest and other cell populations in embryonic development. We have shown that one such boundary, an interface between cranial neural crest and mesoderm in the developing skull, is crucial for proper growth and patterning of the calvarial bones. We have also identified genes in mice and humans that control this boundary. These include the transcription factor Twist1, which controls the boundary through the signaling molecules, EphA4, and Jagged1. Mutations in each of these genes cause human disorders that affect the development of the skull. Current topics under study include genetic and epigenetic factors controlling neural crest stem cell development and the role of ephrin and notch signaling in osteogenic precursor cell migration and specification. Our interest in cancer centers on the role of the Brca1 gene in ovarian cancer, and more recently, the characterization of the 8q24 locus in humans. This locus contains several conserved elements that function as enhancers and are capable of directing expression in specific tissues in which cancers develop, including breast and prostate. Current topics under study include the identification of genes regulated by the 8q24 enhancers.

Publications

Sun J, Ting MC, Ishii M, Maxson R. Msx1 and Msx2 function together in the regulation of primordial germ cell migration in the mouse. Dev Biol. 2016 Sep 1; 417(1):11-24. View in: PubMed

Wang J, Xiao Y, Hsu CW, Martinez-Traverso IM, Zhang M, Bai Y, Ishii M, Maxson RE, Olson EN, Dickinson ME, Wythe JD, Martin JF. Yap and Taz play a crucial role in neural crest-derived craniofacial development. Development. 2016 Feb 1; 143(3):504-15. View in: PubMed

Liu Y, Yen HY, Austria T, Pettersson J, Peti-Peterdi J, Maxson R, Widschwendter M, Dubeau L. A Mouse Model That Reproduces the Developmental Pathways and Site Specificity of the Cancers Associated With the Human BRCA1 Mutation Carrier State. EBioMedicine. 2015 Oct; 2(10):1318-30. View in: PubMed

Liu Y, Pike MC, Wu N, Lin YG, Mucowski S, Punj V, Tang Y, Yen HY, Stanczyk FZ, Enbom E, Austria T, Widschwendter M, Maxson R, Dubeau L. Brca1 Mutations Enhance Mouse Reproductive Functions by Increasing Responsiveness to Male-Derived Scent. PLoS One. 2015; 10(10):e0139013. View in: PubMed

Ishii M, Sun J, Ting MC, Maxson RE. The Development of the Calvarial Bones and Sutures and the Pathophysiology of Craniosynostosis. Curr Top Dev Biol. 2015; 115:131-56. View in: PubMed

Cheng SL, Behrmann A, Shao JS, Ramachandran B, Krchma K, Bello Arredondo Y, Kovacs A, Mead M, Maxson R, Towler DA. Targeted Reduction of Vascular Msx1 and Msx2 Mitigates Arteriosclerotic Calcification and Aortic Stiffness in LDLR-Deficient Mice Fed Diabetogenic Diets. Diabetes. 2014 Dec; 63(12):4326-37. View in: PubMed

Yumoto K, Thomas PS, Lane J, Matsuzaki K, Inagaki M, Ninomiya-Tsuji J, Scott GJ, Ray MK, Ishii M, Maxson R, Mishina Y, Kaartinen V. TGF-ß-activated kinase 1 (Tak1) mediates agonist-induced Smad activation and linker region phosphorylation in embryonic craniofacial neural crest-derived cells. J Biol Chem. 2013 May 10; 288(19):13467-80. View in: PubMed

Cha J, Sun X, Bartos A, Fenelon J, Lefèvre P, Daikoku T, Shaw G, Maxson R, Murphy BD, Renfree MB, Dey SK. A new role for muscle segment homeobox genes in mammalian embryonic diapause. Open Biol. 2013 Apr; 3(4):130035. View in: PubMed

Sun J, Ishii M, Ting MC, Maxson R. Foxc1 controls the growth of the murine frontal bone rudiment by direct regulation of a Bmp response threshold of Msx2. Development. 2013 Mar; 140(5):1034-44. View in: PubMed

Sharma VP, Fenwick AL, Brockop MS, McGowan SJ, Goos JA, Hoogeboom AJ, Brady AF, Jeelani NO, Lynch SA, Mulliken JB, Murray DJ, Phipps JM, Sweeney E, Tomkins SE, Wilson LC, Bennett S, Cornall RJ, Broxholme J, Kanapin A. Mutations in TCF12, encoding a basic helix-loop-helix partner of TWIST1, are a frequent cause of coronal craniosynostosis. Nat Genet. 2013 Mar; 45(3):304-7. View in: PubMed

Ishii M, Arias AC, Liu L, Chen YB, Bronner ME, Maxson RE. A stable cranial neural crest cell line from mouse. Stem Cells Dev. 2012 Nov 20; 21(17):3069-80. View in: PubMed

Yen HY, Gabet Y, Liu Y, Martin A, Wu NL, Pike MC, Frenkel B, Maxson R, Dubeau L. Alterations in Brca1 expression in mouse ovarian granulosa cells have short-term and long-term consequences on estrogen-responsive organs. Lab Invest. 2012 Jun; 92(6):802-11. View in: PubMed

Ting MC, Liao CP, Yan C, Jia L, Groshen S, Frenkel B, Roy-Burman P, Coetzee GA, Maxson R. An enhancer from the 8q24 prostate cancer risk region is sufficient to direct reporter gene expression to a subset of prostate stem-like epithelial cells in transgenic mice. Dis Model Mech. 2012 May; 5(3):366-74. View in: PubMed

Daikoku T, Cha J, Sun X, Tranguch S, Xie H, Fujita T, Hirota Y, Lydon J, DeMayo F, Maxson R, Dey SK. Conditional deletion of Msx homeobox genes in the uterus inhibits blastocyst implantation by altering uterine receptivity. Dev Cell. 2011 Dec 13; 21(6):1014-25. View in: PubMed

Yen HY, Ting MC, Maxson RE. Jagged1 functions downstream of Twist1 in the specification of the coronal suture and the formation of a boundary between osteogenic and non-osteogenic cells. Dev Biol. 2010 Nov 15; 347(2):258-70. View in: PubMed

Roybal PG, Wu NL, Sun J, Ting MC, Schafer CA, Maxson RE. Inactivation of Msx1 and Msx2 in neural crest reveals an unexpected role in suppressing heterotopic bone formation in the head. Dev Biol. 2010 Jul 1; 343(1-2):28-39. View in: PubMed

Pace DA, Maxson R, Manahan DT. Ribosomal analysis of rapid rates of protein synthesis in the Antarctic sea urchin Sterechinus neumayeri. Biol Bull. 2010 Feb; 218(1):48-60. View in: PubMed

Hong H, Yen HY, Brockmeyer A, Liu Y, Chodankar R, Pike MC, Stanczyk FZ, Maxson R, Dubeau L. Changes in the mouse estrus cycle in response to BRCA1 inactivation suggest a potential link between risk factors for familial and sporadic ovarian cancer. Cancer Res. 2010 Jan 1; 70(1):221-8. View in: PubMed

Asahina K, Tsai SY, Li P, Ishii M, Maxson RE, Sucov HM, Tsukamoto H. Mesenchymal origin of hepatic stellate cells, submesothelial cells, and perivascular mesenchymal cells during mouse liver development. Hepatology. 2009 Mar; 49(3):998-1011. View in: PubMed

Ting MC, Wu NL, Roybal PG, Sun J, Liu L, Yen Y, Maxson RE. EphA4 as an effector of Twist1 in the guidance of osteogenic precursor cells during calvarial bone growth and in craniosynostosis. Development. 2009 Mar; 136(5):855-64. View in: PubMed

Plikus MV, Widelitz RB, Maxson R, Chuong CM. Analyses of regenerative wave patterns in adult hair follicle populations reveal macro-environmental regulation of stem cell activity. Int J Dev Biol. 2009; 53(5-6):857-68. View in: PubMed

Li P, Tong C, Mehrian-Shai R, Jia L, Wu N, Yan Y, Maxson RE, Schulze EN, Song H, Hsieh CL, Pera MF, Ying QL. Germline competent embryonic stem cells derived from rat blastocysts. Cell. 2008 Dec 26; 135(7):1299-310. View in: PubMed

Plikus MV, Mayer JA, de la Cruz D, Baker RE, Maini PK, Maxson R, Chuong CM. Cyclic dermal BMP signalling regulates stem cell activation during hair regeneration. Nature. 2008 Jan 17; 451(7176):340-4. View in: PubMed

Maxson R, Ishii M. The Bmp pathway in skull vault development. Front Oral Biol. 2008; 12:197-208. View in: PubMed

Chen YH, Ishii M, Sucov HM, Maxson RE. Msx1 and Msx2 are required for endothelial-mesenchymal transformation of the atrioventricular cushions and patterning of the atrioventricular myocardium. BMC Dev Biol. 2008; 8:75. View in: PubMed

Han J, Ishii M, Bringas P, Maas RL, Maxson RE, Chai Y. Concerted action of Msx1 and Msx2 in regulating cranial neural crest cell differentiation during frontal bone development. Mech Dev. 2007 Sep-Oct; 124(9-10):729-45. View in: PubMed

Chen YH, Ishii M, Sun J, Sucov HM, Maxson RE. Msx1 and Msx2 regulate survival of secondary heart field precursors and post-migratory proliferation of cardiac neural crest in the outflow tract. Dev Biol. 2007 Aug 15; 308(2):421-37. View in: PubMed

Fu H, Ishii M, Gu Y, Maxson R. Conditional alleles of Msx1 and Msx2. Genesis. 2007 Aug; 45(8):477-81. View in: PubMed

Chai Y, Maxson RE. Recent advances in craniofacial morphogenesis. Dev Dyn. 2006 Sep; 235(9):2353-75. View in: PubMed

Merrill AE, Bochukova EG, Brugger SM, Ishii M, Pilz DT, Wall SA, Lyons KM, Wilkie AO, Maxson RE. Cell mixing at a neural crest-mesoderm boundary and deficient ephrin-Eph signaling in the pathogenesis of craniosynostosis. Hum Mol Genet. 2006 Apr 15; 15(8):1319-28. View in: PubMed

Ishii M, Han J, Yen HY, Sucov HM, Chai Y, Maxson RE. Combined deficiencies of Msx1 and Msx2 cause impaired patterning and survival of the cranial neural crest. Development. 2005 Nov; 132(22):4937-50. View in: PubMed

Liu W, Selever J, Murali D, Sun X, Brugger SM, Ma L, Schwartz RJ, Maxson R, Furuta Y, Martin JF. Threshold-specific requirements for Bmp4 in mandibular development. Dev Biol. 2005 Jul 15; 283(2):282-93. View in: PubMed

Maxson R. Adaptation: a developmental biologist in the Antarctic. Genesis. 2005 Jul; 42(3):117-23. View in: PubMed

Chodankar R, Kwang S, Sangiorgi F, Hong H, Yen HY, Deng C, Pike MC, Shuler CF, Maxson R, Dubeau L. Cell-nonautonomous induction of ovarian and uterine serous cystadenomas in mice lacking a functional Brca1 in ovarian granulosa cells. Curr Biol. 2005 Mar 29; 15(6):561-5. View in: PubMed

Brugger SM, Merrill AE, Torres-Vazquez J, Wu N, Ting MC, Cho JY, Dobias SL, Yi SE, Lyons K, Bell JR, Arora K, Warrior R, Maxson R. A phylogenetically conserved cis-regulatory module in the Msx2 promoter is sufficient for BMP-dependent transcription in murine and Drosophila embryos. Development. 2004 Oct; 131(20):5153-65. View in: PubMed

Ishii M, Merrill AE, Chan YS, Gitelman I, Rice DP, Sucov HM, Maxson RE. Msx2 and Twist cooperatively control the development of the neural crest-derived skeletogenic mesenchyme of the murine skull vault. Development. 2003 Dec; 130(24):6131-42. View in: PubMed

Wu LY, Li M, Hinton DR, Guo L, Jiang S, Wang JT, Zeng A, Xie JB, Snead M, Shuler C, Maxson RE, Liu YH. Microphthalmia resulting from MSX2-induced apoptosis in the optic vesicle. Invest Ophthalmol Vis Sci. 2003 Jun; 44(6):2404-12. View in: PubMed

Ma L, Liu J, Wu T, Plikus M, Jiang TX, Bi Q, Liu YH, Müller-Röver S, Peters H, Sundberg JP, Maxson R, Maas RL, Chuong CM. 'Cyclic alopecia' in Msx2 mutants: defects in hair cycling and hair shaft differentiation. Development. 2003 Jan; 130(2):379-89. View in: PubMed

Jiang X, Choudhary B, Merki E, Chien KR, Maxson RE, Sucov HM. Normal fate and altered function of the cardiac neural crest cell lineage in retinoic acid receptor mutant embryos. Mech Dev. 2002 Sep; 117(1-2):115-22. View in: PubMed

Jiang X, Iseki S, Maxson RE, Sucov HM, Morriss-Kay GM. Tissue origins and interactions in the mammalian skull vault. Dev Biol. 2002 Jan 1; 241(1):106-16. View in: PubMed

Kwang SJ, Brugger SM, Lazik A, Merrill AE, Wu LY, Liu YH, Ishii M, Sangiorgi FO, Rauchman M, Sucov HM, Maas RL, Maxson RE. Msx2 is an immediate downstream effector of Pax3 in the development of the murine cardiac neural crest. Development. 2002 Jan; 129(2):527-38. View in: PubMed

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