Dimerization-driven degradation of <i>C. elegans</i> and human E proteins

Sallee, Maria D.; Greenwald, Iva

doi:10.1101/gad.261917.115

Cited by 35 publications

(81 citation statements)

References 35 publications

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“…At the outset of this study, we knew that hlh-2 is critical for the development of all of the regulatory cells [4–8], that HLH-2, like all E proteins, functions in a dimer [16,17], and that HLH-2 acts as a homodimer for specification and function of the AC [18]. As E proteins more commonly form heterodimers with other bHLH proteins, we expected that heterodimers would mediate various roles in other regulatory cells, but other than a requirement for HLH-12:HLH-2 heterodimers for full outgrowth of gonad arms [7], no other bHLH partners had been implicated in regulatory cell specification or function.…”

Section: Resultsmentioning

confidence: 99%

“…In hermaphrodites, this marker, a fragment of the hlh-2 promoter, is expressed in the four proximal cells of the somatic gonad primordium that have the potential to be the AC (the “α” cells and their sisters; Fig. 1), and remains strongly expressed in the committed AC; it is not expressed in the committed LC or cells with LC potential, hDTCs, or mDTCs ([18], Fig. 4A).…”

Section: Resultsmentioning

confidence: 99%

“…The timing and specificity of reporters for hlh-2 and the bHLH genes encoding its dimerization partners suggest that their regulatory regions integrate these inputs. Indeed, a specific element of the hlh-2 promoter region, hlh-2 prox, is necessary and sufficient for its expression in the AC and its precursors in a wild-type hermaphrodite ([18], Fig. 4A).…”

Section: Resultsmentioning

confidence: 99%

“…The AC provides a tabula rasa for such an “addition experiment” because HLH-2 functions as a homodimer to specify its fate and functions, and there is no evidence for any potential dimerization partner by function or expression [18]. We therefore tested if we could switch the identity of the AC, which has a proximal lineage origin and a female sexual identity, to the mDTC, which has a distal lineage origin and a male sexual identity.…”

Section: Resultsmentioning

confidence: 99%

“…It is known that HLH-2 homodimers directly regulate many different genes in the anchor cell [5,18,32–34]. It is intriguing that HLH-12 is expressed in hDTCs and the LC, which both have leader function, and at least two genes required for outgrowth appear to be bHLH transcriptional targets [7,35].…”

Section: Discussionmentioning

confidence: 99%

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A bHLH Code for Sexually Dimorphic Form and Function of the C. elegans Somatic Gonad

2017

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Summary How sexually dimorphic gonads are generated is a fundamental question at the interface of developmental and evolutionary biology [1–3]. In C. elegans, sexual dimorphism in gonad form and function largely originates in different apportionment of roles to three “regulatory cells” of the somatic gonad primordium in young larvae. Their essential roles include leading gonad arm outgrowth, serving as the germline niche, connecting to epithelial openings, and organizing reproductive organ development. The development and function of the regulatory cells in both sexes requires the basic Helix-Loop-Helix (bHLH) transcription factor HLH-2, the sole ortholog of the E proteins mammalian E2A and Drosophila Daughterless [4–8], yet how they adopt different fates to execute their different roles has been unknown. Here, we show that each regulatory cell expresses a distinct complement of bHLH-encoding genes--and therefore distinct HLH-2:bHLH dimers--and formulate a “bHLH code” hypothesis for regulatory cell identity. We support this hypothesis by showing that the bHLH gene complement is both necessary and sufficient to confer particular regulatory cell fates. Strikingly, prospective regulatory cells can be directly reprogrammed into other regulatory cell types simply by loss or ectopic expression of bHLH genes, and male-to-female and female-to-male transformations indicate that the code is instructive for sexual dimorphism. The “bHLH code” appears to be embedded in a bow-tie regulatory architecture [9,10], wherein sexual, positional, temporal, and lineage inputs connect through bHLH genes to diverse outputs for terminal features, and provides a plausible mechanism for the evolutionary plasticity of gonad form seen in nematodes [11–15].

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