Cis-regulatory logic driving glial cells missing: Self-sustaining circuitry in later embryogenesis
- Creators
- Ransick, Andrew
- Davidson, Eric H.
Abstract
The glial cells missing (gcm) regulatory gene of the sea urchin Strongylocentrotus purpuratus is first expressed in veg2 daughter cells as the genomic target of late cleavage stage Delta-Notch signaling from the skeletogenic mesoderm precursors. Gcm is required in veg2 progeny during late cleavages for the early phase of pigment cell precursor specification. Here we report on a later acting cis-regulatory module that assumes control of gcm expression by the early mesenchyme blastula stage and maintains it through pigment cell differentiation and dispersal. Cis-perturbation analyses reveal that the two critical elements within this late module are consensus matches to Gcm and Six1 binding sites. Significantly, six1 mRNA localizes to gcm + cells from the mesenchyme blastula stage onwards. Trans-perturbations with anti-sense morpholinos reveal a co-dependency between six1 and gcm. Six1 mRNA levels fall sharply after Gcm is depleted, while depleting Six1 leads to significant reductions in output of endogenous gcm or modular-reporters. These results support the conclusion gcm and six1 comprise a positive intergenic feedback loop in the mesodermal GRN. This often employed cross regulatory GRN feature here ensures self-sustaining gcm output in a cohort of fully specified pigment cell precursors at a relatively early developmental stage.
Additional Information
© 2012 Elsevier Inc. Received 4 October 2011. Revised 20 January 2012. Accepted 2 February 2012. Available online 13 February 2012. We are pleased to acknowledge Stefan Materna for helpful discussions and for sharing his mesodermal GRN data prior to its publication; Julie Hahn and Ping Dong for BAC constructs, and the labs of S. Fraser, E. Rothenberg and B. Wold for sharing resources. This work is supported by NIH grant HD-37105.Attached Files
Accepted Version - nihms357093.pdf
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Additional details
- PMCID
- PMC3561781
- Eprint ID
- 30104
- Resolver ID
- CaltechAUTHORS:20120416-131358867
- HD-37105
- NIH
- Created
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2012-04-17Created from EPrint's datestamp field
- Updated
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2021-11-09Created from EPrint's last_modified field