Histone deacetylase (Rpd3) regulates Drosophila early brain development via regulation of Tailless.

Manika Pal Bhadra,Paromita Das

doi:10.1098/rsob.200029

Abstract

Tailless is a committed transcriptional repressor and principal regulator of the brain and eye development in Drosophila. Rpd3, the histone deacetylase, is an established repressor that interacts with co-repressors like Sin3a, Prospero, Brakeless and Atrophin. This study aims at deciphering the role of Rpd3 in embryonic segmentation and larval brain development in Drosophila. It delineates the mechanism of Tailless regulation by Rpd3, along with its interacting partners. There was a significant reduction in Tailless in Rpd3 heteroallelic mutant embryos, substantiating that Rpd3 is indispensable for the normal Tailless expression. The expression of the primary readout, Tailless was correlative to the expression of the neural cell adhesion molecule homologue, Fascilin2 (Fas2). Rpd3 also aids in the proper development of the mushroom body. Both Tailless and Fas2 expression are reported to be antagonistic to the epidermal growth factor receptor (EGFR) expression. The decrease in Tailless and Fas2 expression highlights that EGFR is upregulated in the larval mutants, hindering brain development. This study outlines the axis comprising Rpd3, dEGFR, Tailless and Fas2, which interact to fine-tune the early segmentation and larval brain development. Therefore, Rpd3 along with Tailless has immense significance in early embryogenesis and development of the larval brain.

Highlights

IntroductionThe co-repressors, Heat shock factor (Hsf ) and Tramtrack (Ttk69), together with GAGA factor (GAF) comprise the dual transcriptional switch that represses tll transcription by binding to the tor response element (tor-RE) at the tll cis-regulatory region
Gap genes are the first subset of the zygotic genes in the Drosophila embryo that is activated under the influence of the maternal factors—Bicoid and Caudal
The present study presented a new role of Rpd3 in regulating the expression of gap genes in the embryos and demonstrated how particular mutations in Rpd3 and its interacting partners affect Tailless expression in the larval brain

Summary

Introduction

The co-repressors, Heat shock factor (Hsf ) and Tramtrack (Ttk69), together with GAGA factor (GAF) comprise the dual transcriptional switch that represses tll transcription by binding to the tor response element (tor-RE) at the tll cis-regulatory region. This repression of tll is relieved when the Torso (Tor) signalling pathway activates Mapk downstream that converts Hsf to an activator and degrades Ttk by phosphorylation [3]. Tailless represses genes from being activated by the epidermal growth factor receptor (EGFR) signalling and/or activates genes that block the reception or execution of such cues. Tailless ensures that the precursor cells achieve the optic lobe fate while a steep increase in EGFR shifts the fate towards Bolwig’s organ formation [4]. tll knockdown in the optic lobe disrupts neurogenesis, producing defective optic ganglia [5]

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