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Biology subjects

Fang, S.

Publications and source records attributed to Fang, S..

3 recordsLinked to original sources

Separable regulation of POW1 in TAF2-mediated grain development and BR-mediated leaf angle formation in rice

Leaf angle is one of the key factors determining rice plant architecture. However, improvement of the leaf angle appears to be unsuccessful in practical breeding because of the simultaneous occurrence of unfavorable traits such as grain size reduction. In this study, we identified the pow1 (put on weight 1) mutant with enlarged grain size and leaf angle, typical brassinosteroid (BR)-related phenotypes caused by excessive cell proliferation and cell expansion. We show that POW1 encodes a novel protein functioning in grain size regulation by repressing the transcription activity of the interacting protein TAF2, a highly conserved member of the transcription initiation complex TFIID. Loss of function of POW1 increases the phosphorylation of OsBZR1 and decreases the inhibitory effect of OsBZR1 on the transcription of BR biosynthesis genes OsDWARF4 (D4) and D11, thus participates in BR-mediated leaf angle regulation. The separable functions of POW1 in grain size and leaf angle control provide a promising strategy to design high-yielding varieties in which both traits would be favorably developed, i.e., compact plant architecture and increased grain size, thus would promote the high-yield breeding a step forward in rice.

developmental biology

A Missense Point Mutation in Nerve Growth Factor (NGFR100W) Results in Selective Peripheral Sensory Neuropathy

A missense point mutation in nerve growth factor (NGFR100W) is associated with hereditary sensory autonomic neuropathy V (HSAN V), originally discovered in a Swedish family. These patients develop severe loss of perception to deep pain but with apparently normal cognitive functions. To better understand the disease mechanism, we have generated the first NGFR100W knockin mouse model of HSAN V. Mice homozygous for the NGFR100W mutation (NGFfln/fln) showed significant structural deficits in intra-epidermal nerve fibers (IENFs) at birth. These mice had a total loss of pain perception at [~]2 months of age and they often failed to survive to full adulthood. Heterozygous mice (NGF+/fln) developed a progressive degeneration of small sensory fibers both behaviorally and functionally: they showed a progressive loss of IENFs starting at the age of 9 months accompanied with progressive loss of perception to painful stimuli such as noxious temperature. Quantitative analysis of lumbar 4/5 dorsal root ganglia (DRG) revealed a significant reduction in small size neurons positive for calcitonin gene-related peptide, while analysis of sciatic nerve fibers revealed the mutant NGF+/fln mice had no reduction in myelinated nerve fibers. Significantly, the amount of NGF secreted from fibroblasts were reduced in heterozygous and homozygous mice compared to their wild-type littermates. Interestingly, NGF+/fln showed no apparent structural alteration in the brain: neither the anterior cingulate cortex nor the medial septum including NGF-dependent basal forebrain cholinergic neurons. Accordingly, these animals did not develop appreciable deficits in tests for central nervous system function. Our study provides novel insights into the selective impact of NGFR100W mutation on the development and function of the peripheral sensory system.

neuroscience

Genome-wide synthetic lethal CRISPR screen identifies FIS1 as a genetic interactor of ALS-linked C9ORF72

Mutations in the C9ORF72 gene are the most common cause of amyotrophic lateral sclerosis (ALS). Both toxic gain of function and loss of function pathogenic mechanisms have been proposed. Accruing evidence from mouse knockout studies point to a role for C9ORF72 as a regulator of immune function. To provide further insight into its cellular function, we performed a genome-wide synthetic lethal CRISPR screen in human myeloid cells lacking C9ORF72. We discovered a strong synthetic lethal genetic interaction between C9ORF72 and FIS1, which encodes a mitochondrial membrane protein involved in mitochondrial fission and mitophagy. Mass spectrometry experiments revealed that in C9ORF72 knockout cells, FIS1 strongly bound to a class of immune regulators that activate the receptor for advanced glycation end (RAGE) products and trigger inflammatory cascades. These findings present a novel genetic interactor for C9ORF72 and suggest a compensatory role for FIS1 in suppressing inflammatory signaling in the absence of C9ORF72.

neuroscience