Systems analysis of circadian time-dependent neuronal epidermal growth factor receptor signaling

Daniel E Zak,Gregory M Miller,Babatunde A Ogunnaike,Haiping Hao,James S Schwaber,Rajanikanth Vadigepalli

doi:10.1186/gb-2006-7-6-r48

Daniel E Zak, Gregory M Miller + Show 4 more

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https://doi.org/10.1186/gb-2006-7-6-r48

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Abstract

A systems level analysis of circadian time-dependent signaling via the epidermal growth factor receptor in the suprachiasmatic nucleus suggests several transcription factors that mediate the transcriptional response to epidermal growth factor receptor signaling.

Highlights

Identifying the gene regulatory networks governing physiological signal integration remains an important challenge in circadian biology
The objectives of the current study were to identify genes responsive to Epidermal growth factor receptor (EGFR) signaling in the suprachiasmatic nuclei (SCN), to determine whether these responses are circadian time dependent, to identify the pathways and functions modulated by EGFR signaling in the SCN, and to make hypotheses about the regulators responsible for the EGFR responses
To generate hypotheses about the pathways and cell functions modulated by EGFR signaling in the SCN, we tested for enrichments of previously established circadian gene expression [17,22] and Gene Ontology (GO) terms in groups of EGF:circadian time (EGF) responsive genes

Summary

Introduction

Identifying the gene regulatory networks governing physiological signal integration remains an important challenge in circadian biology. Epidermal growth factor receptor (EGFR) has been implicated in circadian function and is expressed in the suprachiasmatic nuclei (SCN), the core circadian pacemaker. The transcription networks downstream of EGFR in the SCN are unknown but, by analogy to other SCN inputs, we expect the response to EGFR activation to depend on circadian timing. The present work makes a systems level analysis of contextdependent signaling by the epidermal growth factor receptor (EGFR) in the suprachiasmatic nuclei (SCN). Circadian rhythms are driven by gene regulatory feedback networks [1], and in mammals the SCN comprise the master circadian clock [2]. The effects of phase modulating extracellular inputs to the SCN are regulated by the circadian clock itself and are 'gated' [5] or circadian time dependent. Phases of differential SCN signaling responsiveness cycle with circadian time, and components responsible for circadian modulation of signaling responses must cycle with circadian time, rendering the SCN a interesting and well-contained system for studying context-dependent signaling

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