Professor, Baylor College of Medicine
B.S., Johann Wolfgang Goethe-Universität, Frankfurt am Main, Germany, 1972
Ph.D., Ruprecht-Karls-Universität, Heidelberg, Germany, 1978
Postdoc, Yale University, New Haven, CT 1979-83
Pattern formation and regeneration in mice and Xenopus
The overall aim of our research is to define the molecular basis of embryonic pattern formation. Pattern formation is a process which leads to ordered spatial arrangements of differentiated tissues. It is not only interesting from a theoretical standpoint, but from a medical perspective as well. Each year in USA alone more than 250,000 infants are born with congenital malformation due to incorrect embryonic patterning. It is our goal to identify genes that are involved in pattern formation and characterize developmental processes that lead to correct and incorrect pattern formation. The major research effort in our laboratory is focused on study of homeobox and fork head genes that are involved in the patterning of the embryo. We have identified several genes that are important in early stages of head development
We have found a novel homeobox gene Rx that is essential for normal eye development. Rx is initially expressed in retinal progenitor cells and later in retinal stem cells. Xenopus embryos injected with Rx RNA develop ectopic retinal tissue and display hyperproliferation in the neuroretina. Mouse embryos carrying a null allele of this gene do not form optic cups and consequently do not develop eyes. These observations suggest that Rx regulates the fate or the proliferative abilities of retinal cells and controls the survival of retinal stem cells (Mathers et al., 1997).
We have isolated a Xenopus forkhead gene Xlens1 that is the earliest marker of lens formation and is involved in the control of lens proliferation and differentiation (Kenyon et al., 1999). We have cloned and characterized its murine functional homologue, the forkhead gene Foxe3 that is expressed in the early stages of mouse lens formation. Foxe3, like Xlens1, is expressed in the initial stages of lens induction. It turns off its expression in differentiating fiber cells and remains active only in the relatively undifferentiated, proliferative cells of the anterior lens epithelium. Foxe3 maps to a region on chromosome 4 that contains the dysgenetic lens (dyl) locus. We have found that two mutations in the forkhead box of the Foxe3 allele from dyl mice cause amino acid changes in positions thought to be essential for the structure and function of winged helix domains (Brownell et al., 2000).
Furthermore, we have found that a mutation affecting C-terminal region of the human FOXE3 protein is responsible for anterior segment dysgenesis and cataracts (Semina et al., 2001). We are currently testing gene therapy strategies that would correct this genetic defect.
Zhang L, El-Hodiri HM, Ma HF, Zhang X, Servetnick M, Wensel TG, Jamrich M (2003) Targeted expression of the dominant-negative FGFR4a in the eye using Xrx1A regulatory sequences interferes with normal retinal development. Development 130:4177-4186.
Tseng HT, Shah R, Jamrich M (2004) Function and regulation of FoxF1 during Xenopus gut development. Development 131:3637-3647.
Medina-Martinez O, Brownell I, Amaya-Manzanares F, Hu Q, Behringer RR, Jamrich M (2005) Severe defects in proliferation and differentiation of lens cells in Foxe3 null mice. Molecular and Cellular Biology 25:8854-8863.
Zilinski CA, Shah R, Lane ME, Jamrich M (2005) Modulation of zebrafish pitx3 expression in the primordia of the pituitary, lens, olfactory epithelium and cranial ganglia by hedgehog and nodal signaling. Genesis 41:33-40.
Chou SJ, Hermesz E, Hatta T, Feltner D, El-Hodiri HM, Jamrich M, Mahon K (2006) Conserved regulatory elements establish the dynamic expression of Rpx/HesxI in early vertebrate development. Developmental Biology 292:533-545.
Wang Q, Zhang X, Zhang L, He F, Zhang G, Jamrich M, Wensel TG (2008) Activation-dependent hindrance of photoreceptor G protein diffusion by lipid microdomains. Journal of Biological Chemistry 283:30015-30024.
Swindell EC, Liu C, Shah R, Smith AN, Lang RA, Jamrich M (2008) Eye formation in the absence of retina. Developmental Biology 322:56-64.
Swindell EC, Zilinski CA, Hashimoto R, Shah R, Lane ME, Jamrich M (2008) Regulation and function of foxe3 during early zebrafish development. Genesis 46:177-183.
Medina-Martinez O, Amaya-Manzanares F, Liu C, Mendoza M, Shah R, Zhang L, Behringer RR, Mahon KA, Jamrich M (2009) Cell-autonomous requirement for Rx function in the mammalian retina and posterior pituitary. PLoS One 4:e4513.
Medina-Martinez O, Shah R, Jamrich M (2009) Pitx3 controls multiple aspects of lens development. Developmental Dynamics 238:2193-2201.
McLin VA, Shah R, Desai NP, Jamrich M (2010) Identification and gastrointestinal expression of Xenopus laevis FoxF2. International Journal of Developmental Biology 54:919-924.
Milan Jamrich, Ph.D.
Department of Molecular and Cellular Biology,
Department of Molecular and Human Genetics
Baylor College of Medicine
One Baylor Plaza N620
Houston, Texas 77030, U.S.A.
Tel: (713) 798-3772
Fax: (713) 798-3017