δEF1/ZFH-1 Zn-finger-homeodomain protein. zag-1 mutations cause misexpression of neuron-specific genes, block formation of stereotypic axon branches, perturb neuronal migrations, and induce various axon-guidance,

Cell signaling and cell-intrinsic processes orchestrate the specification and differentiation of distinct neuron types (Edlund and Jessell, 1999). For example, a gradient of sonic hedgehog establishes the expression pattern of different transcriptional regulators along the dorso-ventral axis in the developing, vertebrate ventral spinal cord. The unique complement of factors in each domain determines, in part, the subsequent fate adopted by each neuron. Presumably, it also initiates transcriptional cascades that generate the appropriate characteristics for an individual neuron type, such as axonal structure, synaptic connections and differentiated gene-expression profile. Although factors, such as LIMhomeodomain and ETS-domain proteins, which contribute to the establishment of axonal-projection patterns and connectivity, have been identified in several organisms (reviewed by Hobert and Westphal, 2000; Shirasaki and Pfaff, 2002), the repertoire of factors needed to generate attributes for most neuron types is largely unknown. The nervous system of C. elegans consists of relatively few neurons but it contains a great diversity of neuron types. The 302 neurons of the adult hermaphrodite are grouped classically into 118 classes, based on position, axonal morphology and connectivity (White et al., 1986). Subsequent studies indicate that individual neurons in some classes exhibit different geneexpression profiles, revealing the potential for a still greater number of distinct neuron types (Troemel et al., 1999; Yu et al., 1997). Several genes controlling the formation of neuronspecific characteristics and functional properties have been discovered. Some genes specify the fate of a neuron from an alternative or default state: mutation of the LIM-homeodomain gene lim-4 causes AWB to adopt an AWC-like fate (Sagasti et al., 1999); and mutation of the forkhead domain gene unc-130 induces ASG to adopt an AWA-like fate (Sarafi-Reinach and Sengupta, 2000). Other genes define the characteristics of different neuron types: the homeodomain gene unc-42 regulates axonal development and neuron-type-specific expression of several glutamate and chemosensory receptors (Baran et al., 1999; Brockie et al., 2001); the homeodomain gene unc-30 controls differentiation of GABAergic D-type motor neurons and unc-30 mutants have defects in axon pathfinding, synaptic connectivity and expression of the glutamic acid decarboxylase UNC-25 and GABA vesicular transporter UNC-47 (Eastman et al., 1999; Jin et al., 1994). δEF1/ZFH-1 Zn-finger-homeodomain proteins are distinguished by two arrays of highly similar C2H2-type Znfinger domains and a centrally located homeodomain, and can act as transcriptional repressors through recruitment of the corepressor C-terminal binding protein (CtBP). Although Drosophila has one δ EF1/ZFH-1 homolog (Fortini et al., 1991), vertebrates have two, one of which is most similar to 3781 Development 130, 3781-3794 © 2003 The Company of Biologists Ltd doi:10.1242/dev.00571