Dr Ian Adams: Chromosomes and Gene Expression

The Sdmg1 protein implicated in secretion (green) surrounds the male germ cells in an adult testis

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Germ Cell Development in Mice

 

Summary

Germ cells are responsible for transmitting genetic information from one generation to the next. Meiosis, a specialised form of cell division that halves the number of chromosomes in male and female germ cells, is central to germ cell development and heredity. We are interested in how differences in the timing and regulation of meiosis between male and female germ cells is brought about, and how male and female germ cells protect the genome from mutation.

 

 

 

Key Publications

  1. Best, D.; Sahlender, D.A.; Walther, N.; Peden, A.A. and Adams, I.R. Sdmg1 is a conserved transmembrane protein associated with germ cell sex determination and germline-soma interactions in mice.
    Development 135(8):1415-1425, 2008 PubMed Abstract
  2. Ollinger, R.; Childs, A.J.; Burgess, H.M.; Speed, R.M.; Lundegaard, P.R.; Reynolds, N.; Gray, N.K.; Cooke, H.J. and Adams, I.R. Deletion of the pluripotency-associated Tex19.1 gene causes activation of endogenous retroviruses and defective spermatogenesis in mice.
    PLoS Genet 4(9):e1000199, 2008
    PubMed Abstract
  3. Adams, I.R. and McLaren, A. Sexually dimorphic development of mouse primordial germ cells: switching from oogenesis to spermatogenesis.
    Development     129(5): 1155-1164, 2002
    PubMed Abstract

 

Figure 4. Endogenous retroviruses (purple) are active in Tex19.1 mutant germ cells during meiosis

Endogenous retroviruses (purple) are active in Tex19.1 mutant germ cells during meiosis

 

Recent Publications

  1. Reichmann J, Crichton JH, Madej MJ, Taggart M, Gautier P, Garcia-Perez JL, Meehan RR, Adams IR: Microarray analysis of LTR retrotransposon silencing identifies hdac1 as a regulator of retrotransposon expression in mouse embryonic stem cells. PLoS Comput Biol 8:e1002486, 2012.
    PubMed Abstract
  2. Chassot AA, Gregoire EP, Lavery R, Taketo MM, de Rooij DG, Adams IR, Chaboissier MC: RSPO1/beta-catenin signaling pathway regulates oogonia differentiation and entry into meiosis in the mouse fetal ovary
    PLoS One 6:e25641, 2011.PubMed Abstract
  3. Madsen L, Kriegenburg F, Vala A, Best D, Prag S, Hofmann K, Seeger M, Adams IR, Hartmann-Petersen R: The tissue-specific Rep8/UBXD6 tethers p97 to the endoplasmic reticulum membrane for degradation of misfolded proteins. PLoS One 6:e25061, 2011. PubMed Abstract
  4. Best, D. and Adams, I.R. Sdmg1 is a component of secretory granules in mouse secretory exocrine tissues. Dev Dyn 238(1):223-231, 2009 PubMed Abstract
  5. Kocer, A.; Reichmann, J.; Best, D. and Adams, I.R. Germ Cell Sex Determination in Mammals.
    Mol Hum Reprod 15(4):205-213, 2009 PubMed Abstract

 

Lab Members

Current lab members involved in this work are:

 

Germ cell development in mice

One of the major decisions that germ cells make during their development is whether to differentiate into male sperm or female eggs. Mammalian germ cells decide whether to embark on a male or a female developmental pathway based on signalling molecules present in the embryonic gonad. We are interested in understanding how germ cells interpret these sex-determining signals, and begin their male or female developmental programmes.

 

Recent work in our group suggests that secretion of signalling molecules in the embryonic testis is required for germ cells to decide to develop along a male pathway. Impaired masculinisation of germ cells in the embryo has been implicated in the appearance of testicular germ cell tumours and infertility later in adult life.

 

Male and female germ cells use very different strategies to differentiate into mature haploid gametes, and perhaps as a consequence of this, tend to transmit different types of mutation to the next generation. We are interested in understanding how male and female germ cells maintain the stability of the genome as it is passed from generation to generation. We have recently discovered a novel genetic pathway that protects germ cells from endogenous retroviruses present in the genome, and helps to ensure that the correct number of chromosomes is transmitted to the next generation.

 

Figure 1. Germ cells (arrows) developing in a male (left) or a female (right) embryo. The female germ cells are in meiosis.

Germ cells (arrows) developing in a male (left) or a female (right) embryo. The female germ cells are in meiosis.

 

Purpose

To investigate molecular mechanisms involved in mammalian germ cell development and function.

 

Approach, Progress and Future Work

We use genetic manipulation in pluripotent stem cells in order to investigate genes involved in germ cell development, and variety of techniques in molecular and cell biology to elucidate gene function using appropriate model systems.

 

 

Figure 3. In Tex19.1 mutant germ cells, chromosomes have problems pairing during meiosis (chromosome axes labelled red, paired chromosome axes labelled yellow)

In Tex19.1 mutant germ cells, chromosomes have problems pairing during meiosis (chromosome axes labelled red, paired chromosome axes labelled yellow)