Milan Jamrich, Ph.D.
Professor of Molecular and Human Genetics
B.S., Goethe University Frankfurt, 1972
Ph.D., Ruprecht Karl University, Heidelberg, 1978
Postdoc, Yale University, 1983
The overall aim of our research is to define the molecular basis of embryonic pattern formation. Pattern formation is a process that 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. In the last few years, we have identified several genes that are important in early stages of head development.
We have found that a novel homeobox gene Rx, 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, which 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 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., 2000). We are currently testing gene therapy strategies that would correct this genetic defect.
- Lu F, Kar D, Gruenig N, Zhang ZW, Cousins N, Rodgers HM, Swindell EC, Jamrich M, Schuurmans C, Mathers PH, Kurrasch DM (2013). Rax is a selector gene for mediobasal hypothalamic cell types. J. Neurosci. 33(1): 259-72. doi: 10.1523/JNEUROSCI.0913-12.2013. PubMed PMID: 23283339
- Liu W, Lagutin O, Swindell E, Jamrich M, Oliver G (2010). Neuroretina specification in mouse embryos requires Six3-mediated suppression of Wnt8b in the anterior neural plate. J. Clin. Invest. 120(10): 3568-77. PubMed PMID: 20890044
- 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(2): e4513. PubMed PMID: 19229337
- Swindell EC, Liu C, Shah R, Smith AN, Lang RA, Jamrich M (2008). Eye formation in the absence of retina. Dev. Biol. 322(1): 56-64. PubMed PMID: 18675797
- Medina-Martinez O, Jamrich M (2007). Foxe view of lens development and disease. Development 134(8): 1455-63. PubMed PMID: 17344231
- Wang J, Cortina G, Wu SV, Tran R, Cho JH, Tsai MJ, Bailey TJ, Jamrich M, Ament ME, Treem WR, Hill ID, Vargas JH, Gershman G, Farmer DG, Reyen L, Martin MG (2006). Mutant neurogenin-3 in congenital malabsorptive diarrhea. N. Engl. J. Med. 355(3): 270-80. PubMed PMID: 16855267
- 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. Mol. Cell. Biol. 25(20): 8854-63. PubMed PMID: 16199865
- Van Raay TJ, Moore, KB, Iordanova I, Steele M, Jamrich M, Harris WA, Vetter, ML (2005). Frizzled 5 Signaling Governs the Neural Potential of Progenitors in the Developing Xenopus Retina. Neuron 46(1): 23-36. PubMed PMID: 15820691
- Tseng HT, Shah R, Jamrich M (2004). Function and regulation of FoxF1 during Xenopus gut development. Development 131(15): 3637-47. PubMed PMID: 15229177
- Zhang L, El-Hodiri H, Ma HF, Zhang X, Servetnick M, Wensel TG, Jamrich M (2003). Targeted expression of the dominant negative FGFR-4a in the eye using Xrx1A regulatory sequences interferes with normal retinal cell development. Development 130(17): 4177-86. PubMed PMID: 12874136
- Semina EV, Brownell I, Murray JC, Jamrich M (2001). Mutations in the human forkhead transcription factor FOXE3 are associated with anterior segment ocular dysgenesis and cataracts. Hum. Mol. Genet. 10(3): 231-6. PubMed PMID: 11159941
- Mathers PH, Grinberg A, Mahon KA, Jamrich M (1997). The Rx homeobox gene is essential for vertebrate eye formation. Nature 387(6633): 603-7. PubMed PMID: 9177348
Milan Jamrich, Ph.D.
Department of Molecular and Human Genetics
Baylor College of Medicine
One Baylor Plaza, MS BCM225
Houston, TX, 77030, U.S.A.