For a fertilized egg to develop into an embryo a mass of identical cells must be directed to become a large number of distinct cell types with different functions and then these cells must be organized into functional organs and tissues.
The proteins that direct these crucial events control the expression of an enormous number of genes and are known as transcription factors. Expression of transcription factors is itself tightly controlled and usually only occurs while the developmental step they regulate is taking place. Although many studies have established the importance of turning on a transcription factor at the correct time, few studies have investigated whether it is important when the transcription factor is turned off.
However, new data, generated by Jonathan Epstein and colleagues, at the University of Pennsylvania, Philadelphia, have now indicated that inactivation of transcription factors is important for normal mouse development.
In the study, mice were engineered to express the transcription factor Pax3, which controls the development of cells known as neural crest cells into many different cell types (including some bone cells, some muscle cells, and some nerves), beyond the time it is normally shut off. Defects in craniofacial bone structures derived from neural crest cells were observed in these mice and they died within two days of birth due to cleft or shortened palates.
Detailed analysis revealed that Pax3 prevented neural crest cells from responding to a factor that induces bone development (BMP-2), because it directly upregulated expression of the gene containing the information for making the protein Sostdc1, a soluble inhibitor of BMP signaling. The authors therefore conclude one function of Pax3 is to maintain neural crest cells in an undifferentiated state by preventing them from responding to factors that induce bone development.
Persistent expression of Pax3 in the neural crest causes cleft palate and defective osteogenesis in mice. Journal of Clinical Investigation. May 15, 2008.
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