Urness Lisa D, Li Chaoying, Wang Xiaofen, Mansour Suzanne L
Department of Human Genetics, University of Utah, Salt Lake City, Utah 84112-5330, USA.
Dev Dyn. 2008 Jan;237(1):163-9. doi: 10.1002/dvdy.21380.
The levels of fibroblast growth factor (FGF) signaling play important roles in coordinating development of the mouse inner, middle, and outer ears. Extracellular signal-regulated kinases (ERKs) are among the effectors that transduce the FGF signal to the nucleus and other cellular compartments. Attenuation of ERK activity by dephosphorylation is necessary to modulate the magnitude and duration of the FGF signal. Recently, we showed that inactivation of the ERK phosphatase, dual specificity phosphatase 6 (DUSP6), causes partially penetrant postnatal lethality, hearing loss and skeletal malformations. To determine whether other Dusps may function redundantly with Dusp6 during otic development, we surveyed the expression domains of the three ERK-specific DUSP transcripts, Dusp6, Dusp7, and Dusp9, in the embryonic mouse ear. We show that each is expressed in partially overlapping patterns that correspond to regions of active FGF signaling, suggesting combinatorial roles in negative regulation of this pathway during ear development.
成纤维细胞生长因子（FGF）信号通路的水平在协调小鼠内耳、中耳和外耳的发育过程中发挥着重要作用。细胞外信号调节激酶（ERK）是将FGF信号转导至细胞核及其他细胞区室的效应器之一。通过去磷酸化作用减弱ERK活性对于调节FGF信号的强度和持续时间是必要的。最近，我们发现ERK磷酸酶双特异性磷酸酶6（DUSP6）失活会导致部分出生后致死、听力丧失和骨骼畸形。为了确定在耳发育过程中其他双特异性磷酸酶（Dusps）是否可能与Dusp6发挥冗余功能，我们研究了三种ERK特异性DUSP转录本Dusp6、Dusp7和Dusp9在胚胎小鼠耳中的表达区域。我们发现它们各自以部分重叠的模式表达，这些模式与活跃的FGF信号区域相对应，这表明它们在耳发育过程中对该信号通路的负调控中具有协同作用。
