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The Eck receptor tyrosine kinase is implicated in pattern formation during gastrulation, hindbrain segmentation and
P Ganju1, K Shigemoto, J Brennan
1Ludwig Institute for Cancer Research, London, UK.
Abstract:
Members of the protein superfamily of transmembrane receptor tyrosine kinases are key components of intercellular signal transduction pathways that elicit appropriate cellular responses to environmental cues during development of multicellular organisms. In a search for additional receptor tyrosine kinases expressed during mouse embryogenesis we cloned the murine homolog of Eck, a member of the Eph subfamily, that maps to the distal region of mouse chromosome 4. Specific antisera defined Eck in murine embryonic cells as a glycoprotein of 130 kDa with an intrinsic autophosphorylation activity. Immunohistochemical staining and laser scanning microscopy revealed a dynamic and tightly regulated distribution of Eck receptor protein in the developing mouse embryo. During gastrulation, a high transient distribution of Eck was seen in mesodermal cells aggregating in the midline as notochordal plate. A similar restriction of Eck receptor protein was apparent along the rostrocaudal axis of the developing neural tube. In hindbrain neuroepithelia, Eck protein localised specifically to cells of rhombomere 4 and was also seen transiently in cells populating second and third branchial arches and neurogenic facial crest VII-VIII and IX-X. Receptor distribution also implicated Eck in development of the proximodistal axis of the limb, expression being restricted to distal regions of limb bud mesenchyme. At later stages, additional sites of Eck protein expression were seen in the cartilaginous model of the skeleton, tooth primordia, infundibular component of the pituitary and various fetal tissue epithelia. Taken together, our data suggest pleiotropic functions for the Eck receptor, initially in distinctive aspects of pattern formation and subsequently in development of several fetal tissues, and reveal possible allelism with known mouse developmental mutant loci.
Insights
Researchers identified the Eck receptor tyrosine kinase in mouse embryos, revealing its dynamic expression during development. This protein plays crucial roles in pattern formation and fetal tissue development.
Area of Science:
- Developmental Biology
- Molecular Biology
- Genetics
Background:
- Transmembrane receptor tyrosine kinases (RTKs) are crucial for intercellular signaling in multicellular organisms.
- Eph subfamily RTKs are involved in developmental processes.
- Understanding novel RTKs aids in deciphering developmental pathways.
Purpose of the Study:
- To identify and characterize novel RTKs in mouse embryogenesis.
- To investigate the expression pattern and function of the murine Eck homolog.
- To explore the role of Eck in embryonic development and pattern formation.
Main Methods:
- Cloning of the murine Eck homolog.
- Characterization of Eck protein using specific antisera, defining it as a 130 kDa glycoprotein with autophosphorylation activity.
- Immunohistochemical staining and laser scanning microscopy to visualize Eck distribution in developing mouse embryos.
Main Results:
- Eck expression was dynamic and tightly regulated during embryogenesis.
- High transient Eck distribution observed in mesodermal cells during gastrulation and along the neural tube axis.
- Specific localization in hindbrain neuroepithelia, branchial arches, limb buds, and later in fetal tissues like cartilage, teeth, and pituitary.
Conclusions:
- The Eck receptor exhibits pleiotropic functions in embryonic pattern formation and fetal tissue development.
- Eck's dynamic expression suggests critical roles in cell aggregation, migration, and tissue patterning.
- Further research may reveal allelism with known mouse developmental mutants.