Lovell-Badge group ::

With our demonstration in 1991 that Sry is the Y chromosomal gene that determines sex by switching the development of the embryonic gonad from an ovarian to a testicular fate, the focus of our research has been to understand how Sry achieves this switch in fate. Since Sry encodes a putative transcription factor an obvious but elusive objective has been to identify direct targets for SRY; our results support the view that one such target is Sox9, which like Sry encodes a protein with an "HMG box" DNA binding domain. Our alternative approach has been to study other genes that have been already implicated in sex-reversal phenotypes in mouse or man (e.g. Dax1), or to identify other such genes in mutagenesis screens, and to define where these genes fit in the sex-determining cascade.

Immunostaining of SRY (red) and SOX9 (green) proteins during testis determination ::

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Immunostaining of SRY (red) and SOX9 (green) proteins during the period of testis determination in the mouse. (A) The first SRY-positive cells are seen just below the coelomic epithelium (ce). Subsequently (B,C), in addition to the SRY-positive cells, other cells expressing SRY and SOX9 (yellow) or just SOX 9 are seen, with the proportion that are only positive for SOX9 increasing as development proceeds. It is thought that SRY is directly triggering the up-regulation of Sox9 expression and that once robust SOX9 expression is established, SRY is no longer required, indeed it is actively repressed.

Selected publications ::

• Sekido, R; Bar, I; Narvaez, V; Penny, G and Lovell-Badge, R. (2004)
  SOX9 is up-regulated by the transient expression of SRY specifically in Sertoli cell precursors.
  Developmental Biology 15, 271-9 PubMed abstract
• Rizzoti, K; Brunelli, S; Carmignac, D; Thomas, PQ; Robinson, IC and Lovell-Badge, R (2004)
  SOX3 is required during the formation of the hypothalamo- pituitary axis.
  Nature Genetics 36, 247-255 PubMed abstract
• Avilion, AA; Nicolis, SK; Pevny, LH; Perez, L; Vivian, N and Lovell-Badge, R (2003)
  Multipotent cell lineages in early mouse development depend on SOX2 function.
  Genes and Development 17, 126-140 PubMed abstract
• Hoyle, C; Narvaez, V; Alldus, G; Lovell-Badge, R and Swain, A (2002 )
  Dax1 expression is dependent on steroidogenic factor 1 in the developing gonad.
  Molecular Endocrinology 16, 747-756 PubMed abstract
• Lovell-Badge, R; Canning, C and Sekido, R (2002)
  Sex-determining genes in mice: building pathways.
  Novartis Foundation Symposium 244, 4-22 PubMed abstract
• Lovell-Badge, R (2001)
  The future for stem cell research.
  Nature 414, 88-91 PubMed abstract