Developmental biology

Coordination of chondrogenesis and osteogenesis by fibroblast growth factor 18.Liu, Z. et al. Genes Dev. 16, 859–869 (2002)

FGF18 is required for normal cell proliferation and differentiation during osteogenesis and chondrogenesis. Ohbayashi, N. et al. Genes Dev. 16, 870–879 (2002)

Fibroblast growth factor (FGF) signalling is involved in the development of the vertebrate skeleton. Studies of inherited human skeletal disorders and of mouse knockouts have implicated various FGF receptors (FGFR) in bone and cartilage formation, but until now no ligands have been identified. Now, two papers report that Fgf18 is expressed in the regions of bone formation in the mouse embryo, in areas that overlap with Fgfr3 expression. The possibility that Fgf18 is a ligand for Fgfr3 is supported by the similarity of the two knockout phenotypes — Fgf18−/− embryos have expanded zones of proliferating chondrocytes, and chondrocyte proliferation and differentiation is increased. The delayed ossification seen in Fgf18, but not in Fgfr3 mutants, indicates that Fgf18 probably signals through another FGFR to regulate this process.

Human Disease

Clonally expanded mtDNA point mutations are abundant in individual cells of human tissues.Nekhaeva, E. et al. Proc. Natl Acad. Sci. USA 99, 5521–5526 (2002)

The interest in somatic mitochondrial DNA (mtDNA) mutations derives from their proposed involvement in ageing and tumour development. The phenotypic expression of a mtDNA variant is thought to occur through its clonal expansion in a cell, until it reaches a frequency of ∼90%. Although it has been shown that large mtDNA deletions can be clonally expanded in individual cells, the authors provide the first evidence that the more clinically relevant point mutations can expand in vivo in normal human tissues. By sequencing the mtDNA of individual proliferating and postmitotic cells, they have shown that many cells can accumulate a high proportion of clonally expanded point-mutated mtDNA.

Evolution

The X chromosome is a hot spot for sexually antagonistic fitness variation.Gibson, J. R. et al. Proc. R. Soc. Lond. B 269, 499–505 (2002)

The genome is shaped by different evolutionary forces according to whether it resides in a female or male organism. Theory has it that fitness variation for these sexually antagonistic traits — those that are advantageous for one sex but disadvantageous for the other — are enriched on the X chromosome. Gibson et al. have now provided evidence of this in Drosophila by comparing the fitness variation on 20 cytogenetically cloned X chromosomes to that of the rest of the genome. They show, among other things, that the X chromosome harbours 97% of the sexually antagonistic fitness variation, but only in adults, when the role of the two sexes diverge.