Isoform-Specific Control of Male Neuronal Differentiation and Behavior in Drosophila by the fruitless Gene

Billeter, Jean‐Christophe; Villella, Adriana; Allendorfer, Jane B.; Dornan, Anthony J.; Richardson, Miles; Gailey, Donald A.; Goodwin, Stephen F.

doi:10.1016/j.cub.2006.04.039

Cited by 114 publications

(210 citation statements)

References 45 publications

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“…The shared dorsal cluster of Ilp7 neurons is retained (as in females) but serotonin expression is lost from this region (Fig. 7D,DЈ), as was observed in fru-null males Billeter et al, 2006). Thus, fruM is necessary in males for serotonin expression in dorsal Ilp7 neurons and for the loss of the female-specific Ilp7 neurons.…”

Section: Research Articlesupporting

confidence: 51%

Female-biased dimorphism underlies a female-specific role for post-embryonic Ilp7 neurons inDrosophilafertility

2013

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SUMMARYIn Drosophila melanogaster, much of our understanding of sexually dimorphic neuronal development and function comes from the study of male behavior, leaving female behavior less well understood. Here, we identify a post-embryonic population of Insulin-like peptide 7 (Ilp7)-expressing neurons in the posterior ventral nerve cord that innervate the reproductive tracts and exhibit a female bias in their function. They form two distinct dorsal and ventral subsets in females, but only a single dorsal subset in males, signifying a rare example of a female-specific neuronal subset. Female post-embryonic Ilp7 neurons are glutamatergic motoneurons innervating the oviduct and are required for female fertility. In males, they are serotonergic/glutamatergic neuromodulatory neurons innervating the seminal vesicle but are not required for male fertility. In both sexes, these neurons express the sex-differentially spliced fruitless-P1 transcript but not doublesex. The male fruitless-P1 isoform (fruM) was necessary and sufficient for serotonin expression in the shared dorsal Ilp7 subset, but although it was necessary for eliminating female-specific Ilp7 neurons in males, it was not sufficient for their elimination in females. By contrast, sex-specific RNA-splicing by female-specific transformer is necessary for female-type Ilp7 neurons in females and is sufficient for their induction in males. Thus, the emergence of female-biased post-embryonic Ilp7 neurons is mediated in a subset-specific manner by a tra-and fru-dependent mechanism in the shared dorsal subset, and a tra-dependent, fru-independent mechanism in the female-specific subset. These studies provide an important counterpoint to studies of the development and function of male-biased neuronal dimorphism in Drosophila.

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Section: Research Articlesupporting

confidence: 51%

Female-biased dimorphism underlies a female-specific role for post-embryonic Ilp7 neurons inDrosophilafertility

2013

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“…As transcripts containing exons B and C were found to be conserved, we hypothesise that they are responsible for the essential functions of fru, whereas transcripts containing exons A and D are more likely be involved in non-essential functions, which may contribute to phenotypic differences between species. As exon D does not appear to be included in fru isoforms controlling male sexual behaviour (Billeter et al, 2006b), we further hypothesise that sequence variation in isoforms containing exon A, could influence species-specific differences in male sexual behaviour. We know from molecular genetic studies, that fru exploits these multiple isoforms through spatial and temporal expression of either a single, or a combination of isoforms enabling specific phenotypic outcomes.…”

Section: Discussionmentioning

confidence: 89%

“…We know from molecular genetic studies, that fru exploits these multiple isoforms through spatial and temporal expression of either a single, or a combination of isoforms enabling specific phenotypic outcomes. For instance, the production of serotonergic neurons in the central nervous system that innervate the male reproductive system depends on the expression of Fru MB and Fru MC isoforms and not the Fru MA isoform (Billeter et al, 2006b).…”

Section: Discussionmentioning

confidence: 99%

The evolution of novelty in conserved genes; evidence of positive selection in the Drosophila fruitless gene is localised to alternatively spliced exons

et al. 2013

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There has been much debate concerning whether cis-regulatory or coding changes are more likely to produce evolutionary innovation or adaptation in gene function, but an additional complication is that some genes can dramatically diverge through alternative splicing, increasing the diversity of gene function within a locus. The fruitless gene is a major transcription factor with a wide range of pleiotropic functions, including a fundamental conserved role in sexual differentiation, species-specific morphology and an important influence on male sexual behaviour. Here, we examine the structure of fruitless in multiple species of Drosophila, and determine the patterns of selective constraint acting across the coding region. We found that the pattern of selection, estimated from the ratio of non-synonymous to synonymous substitutions, varied considerably across the gene, with most regions of the gene evolutionarily conserved but with several regions showing evidence of divergence as a result of positive selection. The regions that showed evidence of positive selection were found to be localised to relatively consistent regions across multiple speciation events, and are associated with alternative splicing. Alternative splicing may thus provide a route to gene diversification in key regulatory loci.

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“…In invertebrates, such as fruit flies, male courtship depends on the concerted activities of sexually dimorphic neuronal networks in both the mushroom body (46) and peripheral tissues (39,47). In higher organisms, gonadal hormones are known to exert organizational effects on brain circuits (48).…”

Section: Gh Cells In An Intact Network Show Sex-specific Organized Pamentioning

confidence: 99%

Pituitary growth hormone network responses are sexually dimorphic and regulated by gonadal steroids in adulthood

Sánchez-Cárdenas

Fontanaud

et al. 2010

Proc. Natl. Acad. Sci. U.S.A.

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There are well-recognized sex differences in many pituitary endocrine axes, usually thought to be generated by gonadal steroid imprinting of the neuroendocrine hypothalamus. However, the recognition that growth hormone (GH) cells are arranged in functionally organized networks raises the possibility that the responses of the network are different in males and females. We studied this by directly monitoring the calcium responses to an identical GH-releasing hormone (GHRH) stimulus in populations of individual GH cells in slices taken from male and female murine GH-eGFP pituitary glands. We found that the GH cell network responses are sexually dimorphic, with a higher proportion of responding cells in males than in females, correlated with greater GH release from male slices. Repetitive waves of calcium spiking activity were triggered by GHRH in some males, but were never observed in females. This was not due to a permanent difference in the network architecture between male and female mice; rather, the sex difference in the proportions of GH cells responding to GHRH were switched by postpubertal gonadectomy and reversed with hormone replacements, suggesting that the network responses are dynamically regulated in adulthood by gonadal steroids. Thus, the pituitary gland contributes to the sexually dimorphic patterns of GH secretion that play an important role in differences in growth and metabolism between the sexes. sex hormones | body growth | calcium signaling | systems biology I n most species, males and females display a marked phenotypic divergence in body size, with increased growth rate and body mass being a predominantly masculine trait. Furthermore, in all species examined to date, the growth hormone (GH) axis demonstrates sex-specific differences in hormone contents, secretory outputs, and secretory patterns (1) and their effects on gene expression (2-4). The secretion of GH is controlled by hypothalamic GH-releasing hormone (GHRH) and somatostatin, and there is good evidence for sex-specific imprinting on hypothalamic hypophysiotropic neurons exerted by gonadal steroid exposure early in life (5), with ongoing effects during puberty (6). This has led to the conclusion that the sexually dimorphic control of GH patterns reflects sex differences in GHRH and somatostatin inputs to the pituitary gland. Acute changes in gonadal steroid environment drastically alter the patterns of GH pulsatility in adulthood (7,8); however, although they receive sexually dimorphic inputs (9, 10), GHRH neurons do not display sex-specific electrical characteristics (9, 11). We have previously shown that GH cells in the male mouse pituitary gland form an extensive homotypic cell network with an architecture that exhibits marked plasticity during sexual maturation and that can be altered by gonadectomy (12). Thus, it was important to determine whether male and female pituitary glands would show different responses to the same stimulus in the absence of any hypothalamic influence. To explore this, we assessed the functional activit...

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Isoform-Specific Control of Male Neuronal Differentiation and Behavior in Drosophila by the fruitless Gene

Abstract: This study exemplifies how complex behaviors can be controlled by a single locus through multiple isoforms regulating both developmental and physiological pathways in different neuronal substrates.

Cited by 114 publications

References 45 publications

Female-biased dimorphism underlies a female-specific role for post-embryonic Ilp7 neurons inDrosophilafertility

Female-biased dimorphism underlies a female-specific role for post-embryonic Ilp7 neurons inDrosophilafertility

The evolution of novelty in conserved genes; evidence of positive selection in the Drosophila fruitless gene is localised to alternatively spliced exons

Pituitary growth hormone network responses are sexually dimorphic and regulated by gonadal steroids in adulthood

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