A regulatory cascade of three homeobox genes, ceh-10 ttx-3 and ceh-23, controls cell fate specification of a defined interneuron class in C-elegans

The development of the nervous system requires the coordinated activity of a variety of regulatory factors that define the individual properties of sp ecific neuronal subtypes, We report a regulatory cascade composed of three homeodomain proteins that act to define the properties of a specific intern euron class in the nematode C, elegans, We describe a set of differentiatio n markers characteristic for the AIY interneuron class and show that the ce h-10 paired-type and ttx-3 LIM-type homeobox genes function to regulate all known subtype-specific features of the AIY interneurons, In contrast, the acquisition of several pan-neuronal features is unaffected in ceh-10 and tt x-3 mutants, suggesting that the activity of these homeobox genes separates pan-neuronal from subtype-specific differentiation programs, The LIM homeo box gene ttx-3 appears to play a central role in regulation of AIY differen tiation. Not only are all AIY subtype characteristics lost in ttx-3 mutants , but ectopic misexpression of ttx-3 is also sufficient to induce AIY-like features in a restricted set of neurons. One of the targets of ceh-10 and t tx-3 is a novel type of homeobox gene, ceh-23, We show that ceh-23 is not r equired for the initial adoption of AIY differentiation characteristics, bu t instead is required to maintain the expression of one defined AIY differe ntiation feature. Finally, we demonstrate that the regulatory relationship between ceh-10, ttx-3 and ceh-23 is only partially conserved in other neuro ns in the nervous system, Our findings illustrate the complexity of transcr iptional regulation in the nervous system and provide an example for the in tricate interdependence of transcription factor action.