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Zebrafish Tshz3b negatively regulates Hox function in the developing hindbrain.

Timothy Erickson¹, Laura M Pillay, Andrew J Waskiewicz

¹Department of Biological Sciences, University of Alberta, Edmonton, Canada.

Genesis (New York, N.Y. : 2000)

|June 30, 2011

Summary

Zebrafish tshz3b antagonizes Hox gene function in hindbrain segmentation. This suggests that Teashirt-related proteins conserve their role in repressing Hox genes across species.

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Area of Science:

Developmental Biology
Genetics
Neuroscience

Background:

Teashirt (Tsh) protein regulates trunk segmental identity in flies by repressing anterior Hox genes.
Vertebrate hindbrain patterning relies on Hox paralog group (PG) 1-4 genes.
The function of vertebrate T-box related genes in hindbrain segmentation is unknown.

Purpose of the Study:

Investigate the role of zebrafish tshz3b in hindbrain segmentation.
Determine if tshz3b antagonizes Hox-dependent patterning.
Explore the conserved function of Teashirt-related proteins in regulating Hox gene activity.

Main Methods:

Overexpression analysis in zebrafish embryos.
Structure-function studies of tshz3b.
Analysis of hindbrain segmentation and rhombomere identity.

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Main Results:

Ectopic expression of zebrafish tshz3b disrupts hindbrain segmentation and rhombomere specification.
Tshz3b causes caudal expansion of rhombomere 1 (r1).
Tshz3b functions as a repressor, independent of its homeodomain and unique C-terminal zinc fingers.

Conclusions:

Zebrafish tshz3b antagonizes Hox-dependent hindbrain segmentation.
Negative regulation of Hox PG 1-4 function is a conserved role for Teashirt-related proteins.