Shutdown corner, a large deletion mutant isolated from a haploid mutagenesis screen in zebrafish.

Morphogenesis, the formation of three-dimensional organ structures, requires precise coupling of genetic regulation and complex cell behaviors. The genetic networks governing many morphogenetic systems, including that of the embryonic eye, are poorly understood. In zebrafish, several forward genetic screens have sought to identify factors regulating eye development.

Chromosomal position mediates spinal cord expression of a dbx1a enhancer.

Dbx homeodomain proteins are important for the production of multiple spinal cord cell types. To examine the regulation of Dbx genes in more detail, we have generated transgenic zebrafish in which fluorescent protein expression is driven by predicted dbx1a enhancers. We identified three areas of sequence conservation upstream of the dbx1a coding sequence and generated fluorescent reporter constructs driven by these predicted enhancer elements and the endogenous dbx1a promoter.

Tcf3 inhibits spinal cord neurogenesis by regulating sox4a expression.

The Lef/Tcf factor Tcf3 is expressed throughout the developing vertebrate central nervous system (CNS), but its function and transcriptional targets are uncharacterized. Tcf3 is thought to mediate canonical Wnt signaling, which functions in CNS patterning, proliferation and neurogenesis. In this study, we examine Tcf3 function in the zebrafish spinal cord, and find that this factor does not play a general role in patterning, but is required for the proper expression of Dbx genes in intermediate progenitors.

Proliferation and patterning are mediated independently in the dorsal spinal cord downstream of canonical Wnt signaling.

Canonical Wnt signaling can regulate proliferation and patterning in the developing spinal cord, but the relationship between these functions has remained elusive. It has been difficult to separate the distinct activities of Wnts because localized changes in proliferation could conceivably alter patterning, and gain and loss of function experiments have resulted in both types of defects. To resolve this issue we have investigated canonical Wnt signaling in the zebrafish spinal cord using multiple approaches.

Regulation and function of Dbx genes in the zebrafish spinal cord.

Dbx homeodomain proteins are important for spinal cord dorsal/ventral patterning and the production of multiple spinal cord cell types. We have examined the regulation and function of Dbx genes in the zebrafish. We report that Hedgehog signaling is not required for the induction or maintenance of these genes; in the absence of Hedgehog signaling, dbx1a/1b/2 are expanded ventrally with concomitant increases in postmitotic neurons that differentiate from this domain.