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Interactions of Eph-related receptors and ligands confer rostrocaudal pattern to trunk neural crest migration
Catherine E Krull1, Rusty Lansford, Nicholas W Gale
1Division of Biology and Beckman Institute, California Institute of Technology, Pasadena 91125, USA. cekrull@caltech.edu
Background:
In the trunk of avian embryos, neural crest migration through the somites is segmental, with neural crest cells entering the rostral half of each somitic sclerotome but avoiding the caudal half. Little is known about the molecular nature of the cues-intrinsic to the somites-that are responsible for this segmental migration of neural crest cells.
Results:
We demonstrate that Eph-related receptor tyrosine kinases and their ligands are essential for the segmental migration of avian trunk neural crest cells through the somites. EphB3 localizes to the rostral half-sclerotome, including the neural crest, and the ligand ephrin-B1 has a complementary pattern of expression in the caudal half-sclerotome. To test the functional significance of this striking asymmetry, soluble ligand ephrin-B1 was added to interfere with receptor function in either whole trunk explants or neural crest cells cultured on alternating stripes of ephrin-B1 versus fibronection. Neural crest cells in vitro avoided migrating on lanes of immobilized ephrin-B1; the addition of soluble ephrin-B1 blocked this inhibition. Similarly, in whole trunk explants, the metameric pattern of neural crest migration was disrupted by addition of soluble ephrin-B1, allowing entry of neural crest cells into caudal portions of the sclerotome.
Conclusions:
Both in vivo and in vitro, the addition of soluble ephrin-B1 results in a loss of the metameric migratory pattern and a disorganization of neural crest cell movement. These results demonstrate that Eph-family receptor tyrosine kinases and their transmembrane ligands are involved in interactions between neural crest and sclerotomal cells, mediating an inhibitory activity necessary to constrain neural precursors to specific territories in the developing nervous system.
Insights
Eph receptor tyrosine kinases and ephrin ligands guide avian neural crest cell migration. Blocking ephrin-B1 disrupts this segmental pattern, revealing their role in neural development.
Area of Science:
- Developmental Biology
- Molecular Biology
- Neuroscience
Background:
- Neural crest cell migration in avian embryos is segmental, with cells entering rostral somites but avoiding caudal ones.
- The molecular cues within somites guiding this specific migration pattern are largely unknown.
Purpose of the Study:
- To investigate the role of Eph-related receptor tyrosine kinases and their ligands in the segmental migration of avian trunk neural crest cells.
Main Methods:
- Examined localization of EphB3 receptor and ephrin-B1 ligand in somites.
- Used whole trunk explants and cultured neural crest cells on patterned substrates.
- Interfered with receptor function using soluble ephrin-B1 in vitro and in vivo.
Main Results:
- EphB3 localized to rostral sclerotome and neural crest; ephrin-B1 showed complementary caudal sclerotome expression.
- Neural crest cells avoided migrating on ephrin-B1 substrates in vitro.
- Soluble ephrin-B1 disrupted the segmental migration pattern in whole trunk explants.
Conclusions:
- Eph receptor tyrosine kinases and ephrin ligands are crucial for segmental neural crest migration.
- These interactions mediate inhibitory signals that constrain neural precursors to specific developmental territories.