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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

Altun-Gultekin, Zeynep, Andachi, Yoshiki, Tsalik, Ephraim L., Pilgrim, David, Kohara, Yuji, Hobert, Oliver·2001·Development

DOI 10.1242/dev.128.11.1951

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Abstract

The development of the nervous system requires the coordinated activity of a variety of regulatory factors that define the individual properties of specific neuronal subtypes. We report a regulatory cascade composed of three homeodomain proteins that act to define the properties of a specific interneuron class in the nematode C. elegans. We describe a set of differentiation markers characteristic for the AIY interneuron class and show that the ceh-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 ttx-3 mutants, suggesting that the activity of these homeobox genes separates pan-neuronal from subtype-specific differentiation programs. The LIM homeobox gene ttx-3 appears to play a central role in regulation of AIY differentiation. 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 ttx-3 is a novel type of homeobox gene, ceh-23. We show that ceh-23 is not required for the initial adoption of AIY differentiation characteristics, but instead is required to maintain the expression of one defined AIY differentiation feature. Finally, we demonstrate that the regulatory relationship between ceh-10, ttx-3 and ceh-23 is only partially conserved in other neurons in the nervous system. Our findings illustrate the complexity of transcriptional regulation in the nervous system and provide an example for the intricate interdependence of transcription factor action.

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Authors: Altun-Gultekin, Z., Andachi, Y., Tsalik, E. L., Pilgrim, D., Kohara, Y., & Hobert, O.
Venue: Development
Publisher: The Company of Biologists
Published: 2001-06-01
Volume: 128
Issue: 11
Pages: 1951-1969
ISSN: 0950-1991 (ISSN-L)
1477-9129
DOI: 10.1242/dev.128.11.1951
OpenAlex: W2119646657
Cited by: 286
References: 75
FWCI: 3.58
Type: journal article
Language: en
Open access: closed

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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

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