title: Cis-regulatory logic driving glial cells missing: self-sustaining circuitry in later embryogenesis.
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.
authors.affiliation: California Institute of Technology, Pasadena, CA 91125, USA. andyr@caltech.edu
authors.forename: Andrew
authors.initials: A
authors.lastname: Ransick
authors.forename: Eric H
authors.initials: EH
authors.lastname: Davidson
mesh_terms: D000818:Animals; D001483:Base Sequence; D036703:Blastula / Q000378:metabolism; D004625:Embryo, Nonmammalian / Q000378:metabolism; D047108:Embryonic Development; D005260:Female; D018507:Gene Expression Regulation, Developmental; D005809:Genes, Regulator; D018398:Homeodomain Proteins / Q000235:genetics / Q000378:metabolism*; D008648:Mesoderm / Q000378:metabolism; D008969:Molecular Sequence Data; D009457:Neuroglia / Q000378:metabolism*; D047270:Strongylocentrotus purpuratus / Q000196:embryology*; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*
chemical_list: D018398:Homeodomain Proteins; D014157:Transcription Factors