GO_REF:0000002

Gene Ontology annotation through association of InterPro records with GO terms

GO_REF:0000033

Annotation inferences using phylogenetic trees

GO_REF:0000120

Combined Automated Annotation using Multiple IEA Methods

PMID:18413610

Global regulatory logic for specification of an embryonic cell lineage.

hex is activated, with erg and tgif, immediately downstream of the four double-negative-gate targets (alx1, ets1, tbr, tel) and forms interlocking positive feedback loops with both erg and tgif; knockdown of any one depresses the others.

"These genes are engaged in interlocking positive double feedback loops ( erg with hex ; and hex with tgif ). Interference with expression of any of these genes severely depresses transcript levels of the others ( Fig. S3 ). Thus they dynamically stabilize all aspects of the regulatory state downstream of themselves."
Hex outputs go to tgif, erg, foxo and the skeletogenic differentiation genes.

"In addition to tgif , the outputs of hex go to erg , to differentiation genes as we see below, and to foxo , a late activated regulatory gene the functions of which occur beyond the time frame of this GRN."
hex morphants have a skeleton-minus phenotype with a full complement of ingressed skeletogenic cells, i.e. a differentiation defect without an ingression defect.

"This is not the case for tbr , hex , or tgif : interference with their expression results in embryos with a full complement of ingressed cells of the micromere lineage but these cells are unable to create the biomineral skeleton."
Hex is one of the feed-forward drivers of the biomineralization differentiation gene battery.

"these differentiation genes require as drivers products of all of the now familiar components of the skeletogenic regulatory state ( alx1 , ets1 , tbr , tel , erg , hex , foxb , dri )"

PMID:30264451

From genome to anatomy: The architecture and evolution of the skeletogenic gene regulatory network of sea urchins and other echinoderms.

hex is expressed selectively in the large micromere-PMC lineage and lies downstream of nuclear beta-catenin and pmar1.

"overexpression of pmar1 or a form of cadherin that interferes with β-catenin function have shown that erg, foxN2/3, hex, tel, and tgif are all downstream of β-catenin and pmar1"
The erg/hex/tgif mutual positive interactions are interpreted as converting transient pmar1 expression into a stable skeletogenic regulatory state.

"One prominent example is a set of mutual regulatory interactions among erg, hex, and tgif that reinforces the expression of all three genes."
The ets1 -> hex input reported by Oliveri et al. 2008 was not reproduced by Rafiq et al. 2014.

"Most notably, Oliveri et al. (2008) reported significant changes in the expression of erg, tgif, and hex following Ets1 knockdown, while Rafiq and co-workers (Rafiq et al., 2014) did not detect such changes."

PMID:23261933

Diversification of oral and aboral mesodermal regulatory states in pregastrular sea urchin embryos.

After skeletogenic mesenchyme ingression, hex (with erg and ets1/2) is activated a second time, specifically in the oral non-skeletogenic mesoderm.

"At this time three genes that are first expressed in the SM, erg, hex, and ets1/2 are activated specifically in the oral NSM (Fig. 1O–R)."

PMID:24598159

Sub-circuits of a gene regulatory network control a developmental epithelial-mesenchymal transition.

hex is the sole HHEX-subfamily gene in the sea urchin genome, which supports the identity of the single HHEX-class accession A0A7M7R9J9 with the GRN gene hex.

"All orthologs but hex (hhex) are found within a subfamily of two or three members."
In Lytechinus variegatus, hex is one of the ten downstream PMC transcription factors required for EMT, acting as a terminal node of the apical-constriction and motility sub-circuits.

"apical constriction is controlled by a complex forward cascade that feeds into five terminal TFs: tel, hex, foxn2/3, foxb and foxo."

PMID:17055477

Identification and characterization of homeobox transcription factor genes in Strongylocentrotus purpuratus, and their expression in embryonic development.

Genome-wide survey of the 96 S. purpuratus homeobox genes with QPCR time courses and WMISH; this is the source (ref. 5 of Oliveri et al. 2008) for hex as a homeobox factor of the micromere lineage.

"A set of 96 homeobox transcription factors was identified in the Strongylocentrotus purpuratus genome using permissive blast searches with a large collection of authentic homeodomain sequences from mouse, human and fly."