The transforming growth factor β (TGF-β) family signaling pathway is conserved and ubiquitous in animals. In , fewer representatives of each signaling component are present compared with vertebrates, simplifying mechanistic study of the pathway. Although there are fewer family members, the TGF-β family pathway still regulates multiple and diverse functions in In this review, we focus our attention on several of the classic and best-studied functions for TGF-β family signaling in regulating developmental processes such as embryonic and imaginal disc patterning, but we also describe several recently discovered roles in regulating hormonal, physiological, neuronal, innate immunity, and tissue homeostatic processes.

Speciation constrains the flow of genetic information between populations of sexually reproducing organisms. Gaining control over mechanisms of speciation would enable new strategies to manage wild populations of disease vectors, agricultural pests, and invasive species. Additionally, such control would provide safe biocontainment of transgenes and gene drives. Here, we demonstrate a general approach to create engineered genetic incompatibilities (EGIs) in the model insect Drosophila melanogaster. EGI couples a dominant lethal transgene with a recessive resistance allele. Strains homozygous for both elements are fertile and fecund when they mate with similarly engineered strains, but incompatible with wild-type strains that lack resistant alleles. EGI genotypes can also be tuned to cause hybrid lethality at different developmental life-stages. Further, we demonstrate that multiple orthogonal EGI strains of D. melanogaster can be engineered to be mutually incompatible with wild-type and with each other. EGI is a simple and robust approach in multiple sexually reproducing organisms.

Organ growth and size are finely tuned by intrinsic and extrinsic signaling molecules. In Drosophila, the BMP family member Dpp is produced in a limited set of imaginal disc cells and functions as a classic morphogen to regulate pattern and growth by diffusing throughout imaginal discs. However, the role of TGFβ/Activin-like ligands in disc growth control remains ill-defined. Here we demonstrate that Myoglianin (Myo), an Activin family member, and a close homolog of mammalian Myostatin (Mstn), is a muscle-derived extrinsic factor that uses canonical dSmad2 mediated signaling to regulate wing size. We propose that Myo is a myokine that helps mediate an allometric relationship between muscles and their associated appendages.

24Speciation constrains the flow of genetic information between populations of sexually reproducing 25 organisms. Gaining control over mechanisms of speciation would enable new strategies to manage 26 wild populations of disease vectors, agricultural pests, and invasive species. Additionally, such 27 control would provide safe biocontainment of transgenes and gene drives. Natural speciation can 28 be driven by pre-zygotic barriers that prevent fertilization or by post-zygotic genetic 29 incompatibilities that render the hybrid progeny inviable or sterile. Here we demonstrate a general 30 approach to create engineered genetic incompatibilities (EGIs) in the model insect Drosophila 31 melanogaster. Our system couples a dominant lethal transgene with a recessive resistance allele. 32 EGI strains that are homozygous for both elements are fertile and fecund when they mate with 33 similarly engineered strains, but incompatible with wild-type strains that lack resistant alleles. We 34show that EGI genotypes can be tuned to cause hybrid lethality at different developmental life-35 stages. Further, we demonstrate that multiple orthogonal EGI strains of D. melanogaster can be 36 engineered to be mutually incompatible with wild-type and with each other. Our approach to create 37 EGI organisms is simple, robust, and functional in multiple sexually reproducing organisms. 38 39 Main Text 40In genetics, underdominance occurs when a heterozygous genotype (Aa) is less fit than either 41 homozygous genotype (AA and aa). In 'extreme underdominance', the heterozygote is inviable while 42 each homozygote has equal fitness 1 . Extreme underdominance is an attractive and versatile tool for 43 population control. First, it could be leveraged to create threshold-dependent, spatially-contained 44 gene drives 2 capable of replacing local populations. Such gene drives may be more socially acceptable 45 than threshold-independent gene-drives to suppress populations since their spead can be more tightly 46 controlled. Alternatively, only males could be released for a genetic biocontrol approach that mimics 47 sterile insect technique. Several strategies for engineering underdominance have been described, 48including one-or two-locus toxin-antitoxin systems 3,4 , chromosomal translocations 5 , and RNAi-based 49 negative genetic interactions 6 . Despite its theoretical utility in population control, engineering 50 extreme underdominance has been difficult 1 . 51Extreme underdominance essentially constitutes a speciation event, as it prevents successful 52 reproduction and therefore genetic exchange between two populations. In nature, prezygotic and 53 postzygotic incompatibilities maintain species barriers. Prezygotic incompatibilities prevent 54 fertilization from taking place. These can include geographic separation or behavioral/anatomical 55 differences between individuals in two populations that prevent sperm and egg from meeting. 56Postzygotic incompatibilities occur when genetic or cellular differences between the maternal and 57 paterna...