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Expression of the receptor tyrosine kinase substrate genes eps8 and eps15 during mouse development
V Avantaggiato1, A Torino, W T Wong
1International Institute of Genetics and Biophysics, CNR, Naples, Italy.
Abstract:
Receptor tyrosine kinases (RTKs) control proliferation and differentiation through their ability to bind and/or phosphorylate intracellular substrates. The repertoire of substrates recruited by different RTK is largely overlapping. It is not clear, therefore, how a cell distinguishes among signals originating from different RTKs. One possibility is that selective availability of substrates participates in the regulation of this process. To gain insight into this issue, we studied the expression pattern, during mouse embryogenesis, of the eps8 and eps15 genes, which encode two recently identified RTK substrates. Both genes are expressed from E 10 in a restricted fashion. eps8 is first expressed in frontonasal neural crest-derived cells, in the mesenchyme of branchial arches and in the liver primordium. At E 12.5-E 14, eps8 is additionally expressed in the central nervous system (CNS) in a regional restricted pattern at the met-mesencephalic transition area and in the developing submandibular salivary glands. eps15 is expressed at E 10 in the liver primordium, in the spinal ganglia and in the encephalic ganglia derived from the hindbrain neural crest. In addition, at E 12.5-E 14, eps15 is expressed, along all the CNS, in the ventricular zone where undifferentiated neuroblasts are located. The regional pattern of developmental expression of these two substrates sharply contrasts with their ubiquitous expression in adults, raising the possibility that their expression during embryogenesis is linked to selective proliferative and/or differentiative responses of specific neuroectodermal regions and body organs.
Insights
During mouse embryogenesis, eps8 and eps15 gene expression patterns are restricted, suggesting selective substrate availability regulates receptor tyrosine kinase (RTK) signaling. This contrasts with ubiquitous adult expression, hinting at developmental roles.
Area of Science:
- Developmental biology
- Molecular signaling
- Gene expression analysis
Background:
- Receptor tyrosine kinases (RTKs) regulate cell proliferation and differentiation by interacting with intracellular substrates.
- The overlapping substrate repertoires of different RTKs pose a challenge in understanding signal specificity.
- Selective substrate availability is a potential mechanism for distinguishing RTK-originated signals.
Purpose of the Study:
- To investigate the developmental expression patterns of two RTK substrates, eps8 and eps15, during mouse embryogenesis.
- To explore the hypothesis that restricted expression of RTK substrates contributes to signal specificity.
Main Methods:
- Analysis of eps8 and eps15 gene expression during mouse embryogenesis using established embryonic day (E) staging.
- Detailed mapping of expression domains within various embryonic tissues and structures.
Main Results:
- Both eps8 and eps15 exhibit restricted spatial expression patterns from embryonic day 10 (E10) onwards.
- Specific expression domains include neural crest derivatives, branchial arches, liver primordium, and distinct regions of the central nervous system (CNS).
- Expression patterns differ between eps8 and eps15, with eps15 showing notable localization in the CNS ventricular zone.
Conclusions:
- The temporally and spatially restricted expression of eps8 and eps15 during embryogenesis contrasts with their ubiquitous adult expression.
- These distinct developmental expression profiles suggest a role for selective substrate availability in regulating RTK signaling.
- This mechanism may underlie specific proliferative and differentiative responses in developing neuroectodermal regions and organs.