transforming-growth-factor-beta and Disorders-of-Sex-Development

What is the relationship between reproduction and longevity? Evolutionary biology suggests that reproduction exacts a cost in somatic maintenance, a cost that reduces longevity. The frequent occurrence of this tradeoff between life span and fecundity, both due to experimental manipulations as well as natural variation, suggest that the mechanism might be conserved during evolution. Until recently, little was known about the mechanistic details of how reproduction might regulate life span. Here we discuss recent advances in our understanding of the regulation of life span by reproductive signaling, focusing on studies using Caenorhabditis elegans.

Topics: Aging; Animals; Caenorhabditis elegans; Caenorhabditis elegans Proteins; Cell Lineage; Disorders of Sex Development; Forkhead Transcription Factors; Gene Expression Regulation, Developmental; Genitalia; Germ Cells; Gonads; Insulin; Insulin-Like Growth Factor I; Intestines; Intracellular Signaling Peptides and Proteins; Longevity; Models, Biological; Receptor, Insulin; Receptors, Transforming Growth Factor beta; Reproduction; Signal Transduction; Transcription Factors; Transforming Growth Factor beta

Pheromones elicit innate sex-specific mating behaviors in many species. We demonstrate that in C. elegans, male-specific sexual attraction behavior is programmed in both sexes but repressed in hermaphrodites. Repression requires a single sensory neuron pair, the ASIs. To repress attraction in adults, the ASIs must be present, active, and capable of sensing the environment during development. The ASIs release TGF-β, and ASI function can be bypassed by experimental activation of TGF-β signaling. Sexual attraction in derepressed hermaphrodites requires the same sensory neurons as in males. The sexual identity of both these sensory neurons and a distinct subset of interneurons must be male to relieve repression and release attraction. TGF-β may therefore act to change connections between sensory neurons and interneurons during development to engage repression. Thus, sensation in a single sensory neuron pair during development reprograms a common neural circuit from male to female behavior.

Topics: Animals; Animals, Genetically Modified; Caenorhabditis elegans; Caenorhabditis elegans Proteins; Culture Media, Conditioned; Disorders of Sex Development; Dose-Response Relationship, Drug; Laser Therapy; Male; Pheromones; Sensory Receptor Cells; Sex Characteristics; Sexual Behavior, Animal; Time Factors; Transforming Growth Factor beta

A genetic switch determines whether the indifferent gonad develops into an ovary or a testis. In adult females of many avian species, the left ovary is functional while the right one regresses. In the embryo, bone morphogenetic proteins (BMP) mediate biological effects in many organ developments but their roles in avian sex determination and gonadal differentiation remains largely unknown. Here, we report the sex-specific and left-right (L-R) asymmetric expression pattern of Bmp7 in the chicken gonadogenesis. Bmp7 was L-R asymmetrically expressed at the beginning of genital ridge formation. After sexual differentiation occurred, sex-specific expression pattern of Bmp7 was observed in the ovary mesenchyme. In addition, ovary-specific Bmp7 expression was reduced in experimentally induced female-to-male reversal using the aromatase inhibitor (AI). These dynamic changes of expression pattern of Bmp7 in the gonad with or without AI treatment suggest that BMP may play roles in determination of L-R asymmetric development and sex-dependent differentiation in the avian gonadogenesis.

Topics: Animals; Aromatase Inhibitors; Body Patterning; Bone Morphogenetic Protein 7; Bone Morphogenetic Proteins; Chick Embryo; Disorders of Sex Development; Female; Gonads; Male; Sex Determination Processes; Sex Factors; Transforming Growth Factor beta

We cloned the dbl-1 gene, a C. elegans homolog of Drosophila decapentaplegic and vertebrate BMP genes. Loss-of-function mutations in dbl-1 cause markedly reduced body size and defective male copulatory structures. Conversely, dbl-1 overexpression causes markedly increased body size and partly complementary male tail phenotypes, indicating that DBL-1 acts as a dose-dependent regulator of these processes. Evidence from genetic interactions indicates that these effects are mediated by a Smad signaling pathway, for which DBL-1 is a previously unidentified ligand. Our study of the dbl-1 expression pattern suggests a role for neuronal cells in global size regulation as well as male tail patterning.

Topics: Amino Acid Sequence; Animals; Base Sequence; Body Constitution; Body Patterning; Bone Morphogenetic Proteins; Caenorhabditis elegans; Caenorhabditis elegans Proteins; Cloning, Molecular; Disorders of Sex Development; Epistasis, Genetic; Gene Expression Regulation, Developmental; Genes, Reporter; Genitalia; Male; Molecular Sequence Data; Mutation; Neurons; Neuropeptides; Phenotype; Phylogeny; RNA, Messenger; Sequence Analysis, DNA; Sequence Homology, Amino Acid; Tail; Transforming Growth Factor beta