Ephrin-B1 forward and reverse signaling are required during mouse development

Abstract

Eph receptors and ephrin ligands are key players in many developmental processes including embryo patterning, angiogenesis, and axon guidance. Eph/ephrin interactions lead to the generation of a bidirectional signal, in which both the Eph receptors and the ephrins activate downstream signaling cascades simultaneously. To understand the role of ephrin-B1 and the importance of ephrin-B1-induced reverse signaling during embryonic development, we have generated mouse lines carrying mutations in the efnb1 gene. Complete ablation of ephrin-B1 resulted in perinatal lethality associated with a range of phenotypes, including defects in neural crest cell (NCC)-derived tissues, incomplete body wall closure, and abnormal skeletal patterning. Conditional deletion of ephrin-B1 demonstrated that ephrin-B1 acts autonomously in NCCs, and controls their migration. Last, a mutation in the PDZ binding domain indicated that ephrin-B1-induced reverse signaling is required in NCCs. Our results demonstrate that ephrin-B1 acts both as a ligand and as a receptor in a tissue-specific manner during embryogenesis.

Neuropilin 2/semaphorin 3F signaling is essential for cranial neural crest migration and trigeminal ganglion condensation

“…These will include the neuregulin receptor, ErbB4, which is required non-cell autonomously in the hindbrain to establish the neural crest-free region immediately adjacent to the neural tube at r3 (Golding et al, 2000), and Eph/ephrin signaling. ephrin-B1 is cell autonomously required in neural crest of the third and fourth branchial arch streams for their directional, patterned migration (Davy et al, 2004). In addition, perturbing Xenopus eprhin-B2, EphB1, or EphA4 expression or function leads to branchial arch 3 neural crest migration defects (Smith et al, 1997;Helbling et al, 1998).…”

“…For example, the ephrinB1 transmembrane ligand is cell autonomously required for the direc-tional, patterned migration of neural crest cells in branchial arch streams 3 and 4 but not for the subsequent individualization and condensation of the cranial ganglia (Davy et al, 2004). Eph receptors play a role in patterning these streams as well (Smith et al, 1997;Helbling et al, 1998).…”

Role for ephrinB2 in postnatal lung alveolar development and elastic matrix integrity

“…EphrinB-PDZ interactions have previously been shown to be required for neuronal and neural crest cell migration Davy et al, 2004), and lymphatic vessel remodeling (Makinen et al, 2005), all of which are suggestive of modulations of cellular interaction with the ECM. There are several scenarios (Fig.…”

Candidate regulators of mammary branching morphogenesis identified by genome‐wide transcript analysis

“…4). It was shown previously that ephrin-B1Ϫ/Ϫ mice are perinatally lethal and that ephrin-B1 normally controls neural crest cell migration to target tissues (Davy et al, 2004). Given its expression pattern and its developmental functions, it is possible that ephrin-B1 in mammary gland may regulate TEB motility and/or establish the TEB border at the stromal interface.…”