Zfh1, a somatic motor neuron transcription factor, regulates axon exit from the CNS

Abstract

Motor neurons are defined by their axon projections, which exit the CNS to innervate somatic or visceral musculature, yet remarkably little is known about how motor axons are programmed to exit the CNS. Here, we describe the role of the Drosophila Zfh1 transcription factor in promoting axon exit from the CNS. Zfh1 is detected in all embryonic somatic motor neurons, glia associated with the CNS surface and motor axons, and one identified interneuron. In zfh1 mutants, ventral projecting motor axons often stall at the edge of the CNS, failing to enter the muscle field, despite having normal motor neuron identity. Conversely, ectopic Zfh1 induces a subset of interneurons--all normally expressing two or more "ventral motor neuron transcription factors" (e.g. Islet, Hb9, Nkx6, Lim3)--to project laterally and exit the CNS. We conclude that Zfh1 is required for ventral motor axon exit from the CNS.

Differentiation of the Drosophila serotonergic lineage depends on the regulation of Zfh-1 by Notch and Eagle

“…Ectopic expression of zfh-1 leads to aberrant projections of the EW axons ( Fig. 5B and Layden et al, 2006). We have previously reported a similar mutant phenotype for eg 289 (Lundell and Hirsh, 1998), which we have shown leads to ectopic zfh-1 expression (Fig.…”

“…These results suggest that a loss of Zfh-1 in the GW motor neuron converts it to an EW1 interneuron cell fate and that Zfh-1 is necessary for motor neuron identity in the NB 7-3 lineage. It has previously been suggested that Zfh-1 is not required for specification of cell identity in the CNS (Lai et al, 1993;Layden et al, 2006), clearly this is not the case for the GW motor neuron and there may be other undetected examples.…”

“…Zfh-1 has previously been shown to be expressed in most if not all motor neurons and has been implicated in the differentiation of motor neurons Lai et al, 1991;Layden et al, 2006). Here we show that the GW motor neuron of the NB 7-3 lineage converts to an EW1 interneuron fate in the absence of Zfh-1 (Fig.…”

“…6). Layden et al recently reported that a loss of function in zfh-1 prevents some motor axons from exiting the Drosophila (Layden et al, 2006). A mutation in zag-1, the C. elegans zfh-1 homolog, also shows errors in axon guidance, fasciculation and branching of both motor neurons and interneurons (Clark and Chiu, 2003;Wacker et al, 2003).…”

“…In Drosophila, it is expressed throughout the embryonic mesoderm, mesodermalderived structures, and in the developing CNS including most, if not all, motor neurons Layden et al, 2006). Zfh-1 has been shown to be required for gonad, muscle, and cardiac tissue differentiation as well as axonal guidance Garces and Thor, 2006;Lai et al, 1993;Layden et al, 2006;Moore et al, 1998;Postigo et al, 1999;Su et al, 1999). The C. elegans homolog of Zfh-1, ZAG-1, is expressed both in muscle and the nervous system and is required for differentiation and axonal guidance of both motor neurons and interneurons (Clark and Chiu, 2003;Wacker et al, 2003).…”