The prothoracic gland (PG) of insects plays a key role in sexual maturation; an initial step in this process is body-fat assessment. In Drosophila, the semaphorin gene Sema1a has been shown to play a role in the body-fat sensor mechanism in the prothoracic gland. Multiple genetic reagents have been generated for Sema1a including RNAi-targeting constructs, overexpression constructs, and alleles caused by insertional mutagenesis.
There are multiple genes orthologous to Dmel\Sema1a in human; none has been introduced into flies.
Most loss-of-function phenotypes of Dmel\Sema1a impact neuroanatomy. In contrast, with RNAi targeted to the larval prothoracic gland, larvae with knockdown of Sema1a in the PG fail to initiate maturation despite accruing sufficient fat stores; they continue gaining weight until death after a prolonged third larval instar. A similar phenotype is observed for apolpp (see human disease model report 'obesity and cardiomyocyte regulation of systemic lipid levels, APOB-related' FBhh0001198). This process appears to involve remodeling of endomembranes and control of ribosomal biogenesis. It has been shown that the Sema1a/apolpp body-fat sensor mechanism acts upstream of the cessation of feeding and initiation of sexual maturation triggered by leptin-like upd2 (see human disease model report 'leptin deficiency or dysfunction' FBhh0000503).
[updated Nov. 2021 by FlyBase; FBrf0222196]
Semaphorins are a large family of secreted, transmembrane, or GPI-anchored proteins initially identified as axon guidance cues signaling through their receptors, neuropilins, and plexins. Emerging evidence suggests that semaphorins also function in a broad spectrum of non-neuronal pathophysiological conditions (Hu and Zhu, 2018; pubmed:30405423).
Moderate-scoring ortholog of human SEMA6A and SEMA6D (multiple related genes in both species).
