BACKGROUND Congenital scoliosis is a common type of vertebral malformation. Genetic susceptibility has been implicated in congenital scoliosis. METHODS We evaluated 161 Han Chinese persons with sporadic congenital scoliosis, 166 Han Chinese controls, and 2 pedigrees, family members of which had a 16p11.2 deletion, using comparative genomic hybridization, quantitative polymerase-chain-reaction analysis, and DNA sequencing. We carried out tests of replication using an additional series of 76 Han Chinese persons with congenital scoliosis and a multi-center series of 42 persons with 16p11.2 deletions. RESULTS We identified a total of 17 heterozygous TBX6 null mutations in the 161 persons with sporadic congenital scoliosis (11%); we did not observe any null mutations in TBX6 in 166 controls (P<3.8×10−6). These null alleles include copy-number variants (12 instances of a 16p11.2 deletion affecting TBX6) and single-nucleotide variants (1 nonsense and 4 frame-shift mutations). However, the discordant intrafamilial phenotypes of 16p11.2 deletion carriers suggest that heterozygous TBX6 null mutation is insufficient to cause congenital scoliosis. We went on to identify a common TBX6 haplotype as the second risk allele in all 17 carriers of TBX6 null mutations (P<1.1×10−6). Replication studies involving additional persons with congenital scoliosis who carried a deletion affecting TBX6 confirmed this compound inheritance model. In vitro functional assays suggested that the risk haplotype is a hypomorphic allele. Hemivertebrae are characteristic of TBX6-associated congenital scoliosis. CONCLUSIONS Compound inheritance of a rare null mutation and a hypomorphic allele of TBX6 accounted for up to 11% of congenital scoliosis cases in the series that we analyzed.

Summary Higher plants utilize nucleotide‐binding leucine‐rich repeat domain proteins (NLRs) as intracellular immune receptors to recognize pathogen‐derived effectors and trigger a robust defense. The Activated Disease Resistance 1 (ADR1) family of coiled‐coil NLRs (CNLs) have evolved as helper NLRs that function downstream of many TIR‐type sensor NLRs (TNLs). Close homologs of ADR1s form the N REQUIREMENT GENE 1 (NRG1) family in Arabidopsis, the function of which is unclear. Through CRISPR/Cas9 gene editing methods, we discovered that the tandemly repeated NRG1A and NRG1B are functionally redundant and operate downstream of TNLs with differential strengths. Interestingly, ADR1s and NRG1s function in two distinct parallel pathways contributing to TNL‐specific immunity. Synergistic effects on basal and TNL‐mediated defense were detected among ADR1s and NRG1s. An intact P‐loop of NRG1s is not required for mediating signals from sensor TNLs, whereas auto‐active NRG1A exhibits autoimmunity. Importantly, NRG1s localize to the cytosol and endomembrane network regardless of the presence of effectors, suggesting a cytosolic activation mechanism. Taken together, different sensor TNLs differentially use two groups of helper NLRs, ADR1s and NRG1s, to transduce downstream defense signals.

Summary Grass stomata can balance gas exchange and evaporation effectively in rapidly changing environments via their unique anatomical features. Although the key components of stomatal development in Arabidopsis have been largely elucidated over the past decade, the molecular mechanisms that govern stomatal development in grasses are poorly understood. Via the genome editing system and T‐DNA insertion lines, the key transcriptional factors (TFs) regulating stomatal development in rice (Oryza sativa) were knocked out. A combination of genetic and biochemical assays subsequently revealed the functions of these TFs. OsSPCH/OsICE is essential for the initiation of stomatal lineage. OsMUTE/OsICE determines meristemoid to guard mother cell (GMC) transition. OsFAMA/OsICE influences subsidiary mother cell asymmetric division and mature stoma differentiation. OsFLP regulates the orientation of GMC symmetrical division. More importantly, we found that OsSCR/OsSHR controls the initiation of stomatal lineage cells and the formation of subsidiary cells. The transcription of OsSCR is activated by OsSPCH and OsMUTE. This study characterised the functions of master regulatory TFs that control each stomatal developmental stage in rice. Our findings are helpful for elucidating how various species reprogramme the molecular mechanisms to generate different stomatal types during evolution.

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A protein domain (Toll and Interleukin-1 receptor-like, TIR) with homology to animal Toll and Interleukin-1 receptors mediates immune signaling in prokaryotes and eukaryotes. Here, we present an overview of TIR evolution and the molecular versatility of TIR domains in different protein architectures for host protection against microbial attack in plants. Plant TIR-based signaling emerges as being central to the potentiation and effectiveness of host defenses triggered by intracellular and cell-surface immune receptors. Equally relevant for plant fitness are mechanisms that limit potent TIR signaling in healthy tissues but maintain their preparedness for infection. We propose that seed plants evolved a specialized protein module to selectively translate TIR enzymatic activities to defense outputs, overlaying a more general function of TIRs.

Sexual reproduction plays a critical role in the infection cycle of Fusarium graminearum because ascospores are the primary inoculum. As a homothallic ascomycete, F. graminearum contains both the MAT1-1 and MAT1-2-1 loci in the genome. To better understand their functions and regulations in sexual reproduction and pathogenesis, in this study we assayed the expression, interactions, and mutant phenotypes of individual MAT locus genes. Whereas the expression of MAT1-1-1 and MAT12-1 rapidly increased after perithecial induction and began to decline after 1 day post-perithecial induction (dpi), the expression of MAT1-1-2 and MAT1-1-3 peaked at 4 dpi. MAT1-1-2 and MAT1-1-3 had a similar expression profile and likely are controlled by a bidirectional promoter. Although none of the MAT locus genes were essential for perithecium formation, all of them were required for ascosporogenesis in self-crosses. In outcrosses, the mat11-1-2 and mat11-1-3 mutants were fertile but the mat1-1-1 and mat1-2-1 mutants displayed male- and female-specific defects, respectively. The mat1-2-1 mutant was reduced in FgSO expression and hyphal fusion. Mat1-1-2 interacted with all other MAT locus transcription factors, suggesting that they may form a protein complex during sexual reproduction. Mat1-1-1 also interacted with FgMcm1, which may play a role in controlling cell identity and sexual development. Interestingly, the mat1-1-1 and mat1-2-1 mutants were reduced in virulence in corn stalk rot assays although none of the MAT locus genes was important for wheat infection. The MAT1-1-1 and MAT1-2-1 genes may play a host-specific role in colonization of corn stalks.

TIR signaling promotes the interactions between lipase-like proteins EDS1/PAD4 and ADR1-L1 immune receptor, and oligomerization of ADR1-L1.