FEA2 (FASCIATED EAR2; UniProt Q940E8) is a maize leucine-rich repeat receptor-like protein (LRR-RLP) and the maize ortholog of Arabidopsis CLAVATA2 (CLV2). It is a single-pass type I plasma-membrane protein with a cleaved signal peptide, a large extracellular domain built from ~17-19 leucine-rich repeats (with an internal "island" between LRRs), a single transmembrane helix, and a very short cytoplasmic tail that lacks any obvious intracellular signaling/kinase domain. FEA2 functions in the CLAVATA-WUSCHEL (CLV-WUS) pathway to restrict stem-cell proliferation in shoot and inflorescence meristems: loss-of-function fea2 mutants overproliferate the ear inflorescence meristem (massive fasciation, flattened wider ears with irregular extra rows of seeds) and have a more modest enlargement of floral meristems with increased floral organ number (Taguchi-Shiobara et al. 2001, PMID:11641280). Mechanistically, FEA2 acts as a signal-routing receptor hub at the plasma membrane that perceives distinct CLE peptide ligands and transmits them through two separate downstream effectors: the ZmCLE7 (maize CLV3 ortholog) signal is routed via the heterotrimeric G-protein alpha subunit COMPACT PLANT2 (CT2), whereas the ZmFCP1 signal is routed via the membrane pseudokinase ZmCRN (CORYNE). fea2 mutants are resistant to both CLE peptides, placing FEA2 upstream of both branches; this perception ultimately represses the WUSCHEL ortholog ZmWUS1, restricting meristem size (Je et al. 2018, eLife, doi:10.7554/eLife.35673; Dong et al. 2023; Demesa-Arevalo et al. 2024). FEA2 is expressed in ear primordia, the vegetative apex and young leaves, but not in roots. Because meristem size determines organ number, FEA2 is a quantitative regulator of maize kernel row number (KRN) and a breeding-relevant target for ear architecture (Bommert et al. 2013, PMID:23377180). FEA2 is NOT an enzyme; its molecular role is extracellular CLE-peptide perception/signal transduction, and its core biological role is meristem-size/stem-cell-homeostasis control - not generic cell differentiation.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0030154 cell differentiation | IEA GO_REF:0000043 | MODIFY | Summary: SPKW (GO_REF:0000043) annotation derived from the UniProt keyword "Differentiation" (FEA2 is keyworded "Developmental protein; Differentiation"); snapshot-only, removed in the current GOA release. "Cell differentiation" is a generic catch-all parent term. FEA2's actual role is restriction of stem-cell proliferation and control of meristem size/identity via CLAVATA-CLE signaling, not the broad process of cell differentiation. Reason: GOA's removal of the keyword-derived term was reasonable because "cell differentiation" (GO:0030154) is far too generic and is not the function FEA2 performs. FEA2 is a CLAVATA2-like receptor-like protein that restricts shoot/inflorescence meristem proliferation: fea2 mutants cause a massive overproliferation of the ear inflorescence meristem and increased floral organ number, and FEA2 "normally functions in these meristems to restrict growth" [PMID:11641280]. The genuine biology - maintaining the identity, size and shape of the meristem stem-cell niche by transducing CLE peptide signals (ZmCLE7 via CT2; ZmFCP1 via ZmCRN) to repress ZmWUS1 - is best captured by the meristem-maintenance/meristem-growth ontology branch, not by "cell differentiation". The annotation should therefore be MODIFIED to the more precise term "meristem maintenance" (GO:0010073, "Any process involved in maintaining the identity, size and shape of a meristem"), which complements the already-present "regulation of meristem development" (GO:0048509). The more specific "regulation of meristem growth" (GO:0010075) is also proposed as a NEW term below. Tier A (high-confidence over-broad keyword term replaced by a precise, well-supported meristem term). Proposed replacements: meristem maintenance Supporting Evidence: PMID:11641280 fea2 normally functions in these meristems to restrict growth PMID:11641280 we isolated a novel mutant of maize, fasciated ear2 (fea2), which causes a massive overproliferation of the ear inflorescence meristem and a more modest effect on floral meristem size and organ number file:MAIZE/FEA2/FEA2-deep-research-falcon.md functions at the **plasma membrane** to restrict stem-cell proliferation in shoot and inflorescence meristems |
| GO:0009908 flower development | IBA GO_REF:0000033 | KEEP AS NON CORE | Summary: IBA annotation propagated across the CLV2/FEA2 phylogenetic group. FEA2 affects flower (floral organ) development indirectly, as a consequence of its meristem-size role. Reason: The annotation is correct but represents a secondary/pleiotropic consequence rather than the core function. fea2 mutants have enlarged floral meristems and a consequent increase in floral organ number (extra stamens in male flowers, extra carpels in female flowers), but the paper explicitly interprets this organ-number increase as "presumably a consequence of the enlarged floral meristems" rather than a direct floral-patterning role [PMID:11641280]. The core, mechanistic function is meristem-size restriction via CLAVATA signaling; flower development is downstream of that. Retain as non-core. Supporting Evidence: PMID:11641280 fea2 plants have an increase in floral organ number that is presumably a consequence of the enlarged floral meristems file:MAIZE/FEA2/FEA2-deep-research-falcon.md FEA2 restricts stem-cell proliferation in meristems |
| GO:0048509 regulation of meristem development | IBA GO_REF:0000033 | ACCEPT | Summary: IBA annotation propagated across the CLV2/FEA2 phylogenetic group. This is the core biological process of FEA2: regulation (restriction) of shoot/inflorescence meristem development through CLAVATA-CLE signaling. Reason: This is the central, well-supported function of FEA2 and is at an appropriate level of specificity. FEA2 "regulates shoot meristem proliferation in maize" (UniProt FUNCTION; the title of the cloning paper) and "normally functions in these meristems to restrict growth" [PMID:11641280]. Mechanistically it perceives CLE peptides at the plasma membrane and routes them through CT2 and ZmCRN to repress ZmWUS1, restricting meristem size [file:MAIZE/FEA2/FEA2-deep-research-falcon.md]. The IBA term matches the experimentally demonstrated role; a more specific NEW term (GO:0010075 regulation of meristem growth) is proposed below. Supporting Evidence: PMID:11641280 fea2 normally functions in these meristems to restrict growth file:MAIZE/FEA2/FEA2-deep-research-falcon.md **CLAVATA–WUSCHEL (CLV–WUS)** negative feedback circuit |
| GO:0005886 plasma membrane | IEA GO_REF:0000044 | ACCEPT | Summary: IEA annotation from the UniProt Subcellular-Location keyword mapping (SL-0039, Cell membrane). Correct and confirmed experimentally by FEA2-GFP localization. Reason: Strongly supported. UniProt records the subcellular location as "Cell membrane; Single-pass type I membrane protein", and FEA2 has the predicted topology of an extracellular LRR ectodomain (residues 29-573), a single transmembrane helix (574-597) and a short cytoplasmic tail (598-613). Direct experimental evidence: FEA2 is "predicted to be membrane localized, and visualization of FEA2-GFP is consistent with its targeting to the plasma membrane" [PMID:11641280]. The plasma-membrane location is essential for its role as a receptor for an extracellular CLE-peptide ligand. This IEA duplicates the IDA annotation to the same term and is acceptable. Supporting Evidence: PMID:11641280 FEA2 is predicted to be membrane localized, and visualization of FEA2–GFP is consistent with its targeting to the plasma membrane file:MAIZE/FEA2/FEA2-deep-research-falcon.md functions at the **plasma membrane** to restrict stem-cell proliferation in shoot and inflorescence meristems |
| GO:0005886 plasma membrane | IDA PMID:11641280 The fasciated ear2 gene encodes a leucine-rich repeat recept... | ACCEPT | Summary: IDA annotation from the cloning paper: FEA2-GFP localizes to the plasma membrane. This is the primary experimental evidence for the cellular-component assignment. Reason: Directly supported by experiment. Taguchi-Shiobara et al. visualized a FEA2-GFP fusion and observed accumulation at the plasma membrane, consistent with the predicted single-pass type I topology; they note this "supports the hypothesis that FEA2 acts as a receptor for an extracellular ligand" [PMID:11641280]. (A reproducible secondary fluorescence at the nuclear membrane was noted but its significance was left open and it is not the functional location.) Plasma-membrane localization is core to FEA2's receptor function. Duplicate of the IEA annotation to the same term, which is fine. Supporting Evidence: PMID:11641280 The apparent plasma membrane accumulation of FEA2–GFP supports the hypothesis that FEA2 acts as a receptor for an extracellular ligand PMID:11641280 it encodes a membrane localized leucine-rich repeat receptor-like protein that is most closely related to CLAVATA2 from Arabidopsis |
| GO:0009908 flower development | IMP PMID:11641280 The fasciated ear2 gene encodes a leucine-rich repeat recept... | KEEP AS NON CORE | Summary: IMP annotation from the cloning paper, based on the fea2 mutant phenotype of altered floral organ number. This is a secondary consequence of the meristem-size defect. Reason: The mutant phenotype is real but pleiotropic/downstream. fea2 loss of function produces enlarged floral meristems with a consequent increase in floral organ number (extra stamens and carpels), which the authors explicitly interpret as "presumably a consequence of the enlarged floral meristems" rather than a direct floral developmental function [PMID:11641280]. The disruption phenotype recorded in UniProt likewise lists "increased floral organ numbers" alongside the fasciation/ear phenotypes. Because the essence of FEA2's function is meristem-size restriction, flower development should be kept as a non-core (developmental, pleiotropic) annotation. Supporting Evidence: PMID:11641280 fea2 plants have an increase in floral organ number that is presumably a consequence of the enlarged floral meristems PMID:11641280 Male flowers have an increase in stamen number, and female flowers have an increase in carpel number |
| GO:0048509 regulation of meristem development | IMP PMID:11641280 The fasciated ear2 gene encodes a leucine-rich repeat recept... | ACCEPT | Summary: IMP annotation from the cloning paper: the fea2 loss-of-function mutant overproliferates the inflorescence/floral meristem, demonstrating that FEA2 regulates (restricts) meristem development. This is the core function, supported by direct mutant analysis. Reason: This is the core, experimentally demonstrated function. The fea2 mutant "causes a massive overproliferation of the ear inflorescence meristem and a more modest effect on floral meristem size and organ number", and FEA2 "normally functions in these meristems to restrict growth" [PMID:11641280]. The paper concludes that "the CLAVATA pathway for regulation of meristem size is functionally conserved throughout the angiosperms" [PMID:11641280]. The IMP term is correct and at an appropriate altitude; a more specific NEW term (GO:0010075, regulation of meristem growth) is proposed below to capture the meristem-size specificity. Supporting Evidence: PMID:11641280 which causes a massive overproliferation of the ear inflorescence meristem PMID:11641280 CLAVATA pathway for regulation of meristem size is functionally conserved throughout the angiosperms |
| GO:0001653 peptide receptor activity | IMP PMID:11641280 The fasciated ear2 gene encodes a leucine-rich repeat recept... | NEW | Summary: Proposed NEW molecular-function annotation. FEA2 is the CLV2-like LRR receptor-like protein that perceives secreted CLE peptide ligands (ZmCLE7, ZmFCP1) at the plasma membrane. Current GOA has NO molecular-function term for FEA2 at all. Reason: The current GOA release annotates FEA2 only with biological-process and cellular-component terms and contains no molecular function, even though FEA2's defining role is ligand perception. FEA2 is a membrane LRR receptor-like protein "most closely related to CLAVATA2" whose plasma-membrane localization "supports the hypothesis that FEA2 acts as a receptor for an extracellular ligand" [PMID:11641280]. Mechanistic work established that FEA2 is "a signaling co-receptor/receptor component that perceives CLE peptide signals" - routing ZmCLE7 and ZmFCP1 into distinct downstream effectors, with fea2 mutants resistant to both peptides [file:MAIZE/FEA2/FEA2-deep-research-falcon.md]. "Peptide receptor activity" (GO:0001653, "Combining with an extracellular or intracellular peptide to initiate a change in cell activity") is the accurate MF for a CLE-peptide-perceiving receptor-like protein. (FEA2 lacks a cytoplasmic kinase domain, so a kinase MF is not appropriate; it acts as a receptor/co-receptor module.) IMP/ genetic evidence is justified by the peptide-resistance phenotype of fea2 mutants. Supporting Evidence: PMID:11641280 The apparent plasma membrane accumulation of FEA2–GFP supports the hypothesis that FEA2 acts as a receptor for an extracellular ligand file:MAIZE/FEA2/FEA2-deep-research-falcon.md FEA2 functions as a **shared/co-receptor-like signaling component** in the maize CLV-WUS pathway, restricting stem-cell proliferation in shoot and inflorescence meristems file:MAIZE/FEA2/FEA2-deep-research-falcon.md **fea2 mutants** show resistance to both peptide inputs, supporting the conclusion that FEA2 is required for both pathways |
| GO:0010075 regulation of meristem growth | IMP PMID:11641280 The fasciated ear2 gene encodes a leucine-rich repeat recept... | NEW | Summary: Proposed NEW biological-process annotation capturing the meristem-size specificity of FEA2's function, more precise than the existing GO:0048509 (regulation of meristem development) and a better home for the biology that the retired "cell differentiation" keyword was gesturing at. Reason: FEA2 specifically controls meristem SIZE/growth: fea2 mutants cause "a massive overproliferation of the ear inflorescence meristem" and FEA2 "normally functions in these meristems to restrict growth", with the CLAVATA pathway "for regulation of meristem size" conserved across angiosperms [PMID:11641280]. "Regulation of meristem growth" (GO:0010075, "Any process involved in maintaining the size and shape of a meristem") is more specific than the currently annotated GO:0048509 and directly matches the demonstrated phenotype. Proposed alongside the MODIFY of the retired SPKW term to GO:0010073 (meristem maintenance). IMP justified by the loss-of-function overproliferation phenotype. Supporting Evidence: PMID:11641280 fea2 normally functions in these meristems to restrict growth PMID:11641280 CLAVATA pathway for regulation of meristem size is functionally conserved throughout the angiosperms |
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Download this section (compressed HTML)Q: Does FEA2 directly bind the CLE peptides ZmCLE7 and ZmFCP1, or does it require a co-receptor LRR receptor kinase (analogous to CLV1/BAM) for high-affinity ligand binding, given that FEA2 lacks an intracellular signaling domain?
Suggested experts: David Jackson
Q: How is ligand-specific routing achieved - what determines whether a given CLE peptide signal is transmitted through CT2 (G-protein) versus ZmCRN (pseudokinase)?
Suggested experts: David Jackson, Byoung Il Je
Experiment: In vitro / in planta peptide-binding assays (e.g. photoaffinity labelling or microscale thermophoresis) with purified FEA2 ectodomain and synthetic ZmCLE7 and ZmFCP1 peptides, with and without candidate co-receptor LRR-kinase ectodomains, to determine whether FEA2 binds CLE peptides directly.
Hypothesis: FEA2 perceives CLE peptides as part of a heterodimeric receptor complex and may require a co-receptor LRR receptor kinase for high-affinity binding.
Type: ligand-binding biochemistry
Experiment: Quantitative measurement of ZmWUS1 expression (in situ hybridization / qRT-PCR on microdissected meristems) in wild-type versus fea2, ct2 and Zmcrn single and double mutants, with and without ZmCLE7/ZmFCP1 peptide application.
Hypothesis: FEA2-mediated CLE perception represses ZmWUS1; loss of FEA2 derepresses ZmWUS1, expanding the stem-cell domain and enlarging the meristem.
Type: gene-expression / epistasis analysis
Experiment: Generate and field-test an allelic series of weak FEA2 alleles (cf. the Gly-332/Met-367/Gly-405/Pro-477 mutations) across environments to quantify the dose-response relationship between FEA2 activity, inflorescence meristem size and kernel row number.
Hypothesis: Graded reduction of FEA2 activity tunes meristem size and KRN continuously, making FEA2 a quantitative lever for ear architecture without full fasciation.
Type: quantitative genetics / phenotyping
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