Schwann Cell Development

Neural crest cells also give rise to Schwann cells that line adult peripheral nerves. During development, Schwann cell precursor cells migrate along outgrowing spinal nerve axons where they further differentiate into myelinating and nonmyelinating Schwann cells, both surrounding accompanying axons (Jessen and Mirsky 2005). Neuregulin-1 signals are essential for regulating the migratory capacity of Schwann cell precursors as well. Accordingly, in mice with mutated Neuregulin-1 or ErbB2 genes...

Development of the Neuromuscular Junction

Once myoblasts fuse to form myotubes, they start to synthesize acetylcholine receptor (AChR) subunits that become assembled into functional receptors. Initially, AChRs are homogeneously distributed over the cell surface. With the innervation of the embryonic muscle, AChRs become clustered to membrane regions directly beneath a motor nerve terminal, where the neuromuscular junction (NMJ) forms. In the adult muscle AChRs are approx. 1,000-fold increased at neuromuscular synapses compared to...

The Ligands

NRGs are all characterized by the presence of an extracellular EGF-like domain (Fig. 1). The EGF domain alone is sufficient for activation of ErbB receptor tyrosine kinases. Alternative splicing gives rise to different variants of the EGF domain (a and P) that differ in their affinity to the receptor. By the use of distinct promoters, three major isoforms of the NRG1 gene are generated (Fig. 1) type I NRG-1 (neu differentiation factor, NDF heregulin, HRG acetylcholine receptor inducing...

ErbB3Dependent Functions of Sox10

A systematic analysis of the expression of ErbB3 and Sox10 during embryonic development revealed both genes to be expressed in almost identical spatiotemporal patterns (Britsch et al. 2001). Both genes are expressed in neural crest cells immediately after their birth from the neuroepithelium of the dorsal neural tube. Coexpression of Sox10 and ErbB3 is sustained in primary derivatives of the neural crest, like dorsal root and cranial ganglia anlagen, the primordial sympathetic Soxl0 Dom...

ErbB Receptors in Cancer and Heart Disease

ErbB2 was originally identified because of its oncogenic potential (Hynes and Stern 1994 Olayioye et al. 2000). It was Robert Weinberg's lab that first observed the neu-oncogene to be activated in neuro- and glioblastomas derived from rats treated with the mutagen ethylnitrosourea (EtNU) they showed the neu-oncogene to encode an EGFR-related transmembrane tyrosine kinase receptor (Bargmann et al. 1986). Mutagenesis of rats with ethylnitrosourea was also observed to induce Schwannomas of the...

Neural Crest Cells and Their Derivatives

Neural crest cells constitute a pluripotent embryonic cell population that appears only transiently during development. Neural crest cells are defined by their origins at the lateral borders of the forming neural tube, by their stem-cell-like properties, and by their ability to migrate over long distances along invariant pathways through the embryo. After being specified in the dorsal neural tube epithelium, pre-migratory neural crest cells undergo an epithelio-mesenchymal transition. Such...

Development of the Mammary Gland

Members of the EGF family of signaling molecules have been demonstrated to play critical roles during normal and neoplastic development of the mammary gland. For example, gene targeting experiments in mice revealed essential functions of the EGF-like ligands Amphiregulin, TGFa, and of EGF itself in ductal differentiation and lactogenesis (Luetteke et al. 1999). Several lines of evidence have suggested functions of the Neuregulin signaling system as well (1) Neuregulin-1 can stimulate...