Development (DEVELOPMENT)

Publications in this journal

• Article: The ETS domain transcriptional repressor Anterior open inhibits MAP kinase and Wingless signaling to couple tracheal cell fate with branch identity.

  Sara Caviglia and Stefan Luschnig
  [show abstract] [hide abstract]
  ABSTRACT: Cells at the tips of budding branches in the Drosophila tracheal system generate two morphologically different types of seamless tubes. Terminal cells (TCs) form branched lumenized extensions that mediate gas exchange at target tissues, whereas fusion cells (FCs) form ring-like connections between adjacent tracheal metameres. Each tracheal branch contains a specific set of TCs, FCs, or both, but the mechanisms that select between the two tip cell types in a branch-specific fashion are not clear. Here, we show that the ETS domain transcriptional repressor anterior open (aop) is dispensable for directed tracheal cell migration, but plays a key role in tracheal tip cell fate specification. Whereas aop globally inhibits TC and FC specification, MAPK signaling overcomes this inhibition by triggering degradation of Aop in tip cells. Loss of aop function causes excessive FC and TC specification, indicating that without Aop-mediated inhibition, all tracheal cells are competent to adopt a specialized fate. We demonstrate that Aop plays a dual role by inhibiting both MAPK and Wingless signaling, which induce TC and FC fate, respectively. In addition, the branch-specific choice between the two seamless tube types depends on the tracheal branch identity gene spalt major, which is sufficient to inhibit TC specification. Thus, a single repressor, Aop, integrates two different signals to couple tip cell fate selection with branch identity. The switch from a branching towards an anastomosing tip cell type may have evolved with the acquisition of a main tube that connects separate tracheal primordia to generate a tubular network.
  Development 03/2013;
• Article: The Liguleless narrow mutation affects proximal-distal signaling and leaf growth

  Jihyun Moon, Héctor Candela, Sarah Hake
  [show abstract] [hide abstract]
  ABSTRACT: How cells acquire competence to differentiate according to position is an essential question in developmental biology. Maize leaves provide a unique opportunity to study positional information. In the developing leaf primordium, a line is drawn across a field of seemingly identical cells. Above the line, the cells become blade, below the line the cells become sheath and at the line, the cells differentiate into the specialized tissues of ligule and auricle. We identified a new mutation, Liguleless narrow (Lgn), that affects this patterning and shows striking defects in lateral growth as well, thus linking proximal-distal patterning to medial-lateral growth. In characterizing the defect we discovered that both the auxin transport protein ZmPIN1a and the squamosa promoter-binding protein LIGULELESS1 are expressed precisely at this positionally cued line and are disrupted by Lgn. Positional cloning and a transposon-derived allele demonstrate that LGN is a kinase. These results suggest that LGN participates in setting up positional information through a signaling cascade. Interestingly, LGN has a paralog that is upregulated in the mutant, suggesting an important feedback mechanism involved in setting the positional boundary.
  Development 01/2013; 140:405-412.
• Article: Ephrin-B1 maintains apical adhesion of neural progenitors

  Arvanitis D.N, Behar A, Tryoen-Tóth P, Bush J.O, Jungas T, Vitale N, Davy A
  [show abstract] [hide abstract]
  ABSTRACT: Apical neural progenitors are polarized cells whose apical membrane is the site of cell-cell and cell-extracellular matrix adhesion events that are essential to maintain the integrity of the developing neuroepithelium. Apical adhesion is important for several aspects of the nervous system development including morphogenesis and neurogenesis, yet the mechanisms underlying its regulation remain poorly understood. Herein, we show that ephrin-B1, a cell surface protein that engages in cell signaling upon binding cognate Eph receptors, controls normal morphogenesis of the developing cortex. Efnb1 deficient embryos exhibit morphological alterations of the neuroepithelium which correlate with neural tube closure defects. Using loss-of-function experiments by ex vivo electroporation we demonstrate that ephrin-B1 is required in APs to maintain their apical adhesion. Mechanistically, we show that ephrin-B1 controls cell/ECM adhesion by promoting apical localization of integrin-1 and we identify ADP-ribosylation factor 6 (ARF6) as an important effector of ephrin-B1 reverse signaling in apical adhesion of APs. Our results provide evidence for an important role for ephrin-B1 in maintaining the structural integrity of the developing cortex and highlight the importance of tightly controlling apical cell/ECM adhesion for neuroepithelial development.
  Development 01/2013;
• Article: Dll4-Notch signaling determines the formation of native arterial collateral networks and arterial function in mouse ischemia models

  Brunella Cristofaro, Yu Shi, Marcella Faria, Steven Suchting, Aurelie S. Leroyer, Alexandre Trindade, Antonio Duarte, Ann C. Zovein, M. Luisa Iruela-Arispe, Lina R. Nih, Nathalie Kubis, Daniel Henrion, Laurent Loufrani, Mihail Todiras, Johanna Schleifenbaum, Maik Gollasch, Zhen W. Zhuang, Michael Simons, Anne Eichmann, Ferdinand le Noble
  [show abstract] [hide abstract]
  ABSTRACT: Arteriogenesis requires growth of pre-existing arteriolar collateral networks and determines clinical outcome in arterial occlusive diseases. Factors responsible for the development of arteriolar collateral networks are poorly understood. The Notch ligand Delta- like 4 (Dll4) promotes arterial differentiation and restricts vessel branching. We hypothesized that Dll4 may act as a genetic determinant of collateral arterial networks and functional recovery in stroke and hind limb ischemia models in mice. Genetic loss- and gain-of-function approaches in mice showed that Dll4-Notch signaling restricts pial collateral artery formation by modulating arterial branching morphogenesis during embryogenesis. Adult Dll4+/− mice showed increased pial collateral numbers, but stroke volume upon middle cerebral artery occlusion was not reduced compared with wild-type littermates. Likewise, Dll4+/− mice showed reduced blood flow conductance after femoral artery occlusion, and, despite markedly increased angiogenesis, tissue ischemia was more severe. In peripheral arteries, loss of Dll4 adversely affected excitation-contraction coupling in arterial smooth muscle in response to vasopressor agents and arterial vessel wall adaption in response to increases in blood flow, collectively contributing to reduced flow reserve. We conclude that Dll4-Notch signaling modulates native collateral formation by acting on vascular branching morphogenesis during embryogenesis. Dll4 furthermore affects tissue perfusion by acting on arterial function and structure. Loss of Dll4 stimulates collateral formation and angiogenesis, but in the context of ischemic diseases such beneficial effects are overruled by adverse functional changes, demonstrating that ischemic recovery is not solely determined by collateral number but rather by vessel functionality.
  Development 01/2013;
• Article: Fascin is required for blood cell migration during Drosophila embryogenesis.

  Jennifer Zanet, Brian Stramer, Thomas Millard, Paul Martin, François Payre, Serge Plaza
  [show abstract] [hide abstract]
  ABSTRACT: Fascin is well characterized in vitro as an actin-bundling protein and its increased expression is correlated with the invasiveness of various cancers. However, the actual roles and regulation of Fascin in vivo remain elusive. Here we show that Fascin is required for the invasive-like migration of blood cells in Drosophila embryos. Fascin expression is highly regulated during embryonic development and, within the blood lineage, is specific to the motile subpopulation of cells, which comprises macrophage-like plasmatocytes. We show that Fascin is required for plasmatocyte migration, both as these cells undergo developmental dispersal and during an inflammatory response to epithelial wounding. Live analyses further demonstrate that Fascin localizes to, and is essential for the assembly of, dynamic actin-rich microspikes within plasmatocyte lamellae that polarize towards the direction of migration. We show that a regulatory serine of Fascin identified from in vitro studies is not required for in vivo cell motility, but is crucial for the formation of actin bundles within epithelial bristles. Together, these results offer a first glimpse into the mechanisms regulating Fascin function during normal development, which might be relevant for understanding the impact of Fascin in cancers.
  Development 09/2009; 136(15):2557-65.
• Article: Differential effects of BMP signaling on parvalbumin and somatostatin interneuron differentiation.

  Abhishek Mukhopadhyay, Tammy McGuire, Chian-Yu Peng, John A Kessler
  [show abstract] [hide abstract]
  ABSTRACT: Several different populations of interneurons in the murine cortex, including somatostatin (SST)- or parvalbumin (PV)-expressing cells, are born in the ventral ganglionic eminences during mid-gestation and then migrate tangentially to the cortex. SST is expressed by some interneuron progenitors in the cerebral cortex and in migrating populations in the ventrolateral cortex at birth. However, PV (also known as PVALB) is not expressed by interneurons until the second postnatal week after reaching the cortex, suggesting that molecular cues in the cerebral cortex might be involved in the differentiation process. BMP4 is expressed at high levels in the somatosensory cortex at the time when the PV(+) interneurons differentiate. Treatment of cortical cultures containing interneuron precursors is sufficient to generate PV(+) interneurons prematurely and inhibit SST differentiation. Furthermore, overexpression of BMP4 in vivo increases the number of interneurons expressing PV, with a reduction in the number of SST(+) interneurons. PV(+) interneurons in the cortex express BMP type I receptors and a subpopulation displays activated BMP signaling, assessed by downstream molecules including phosphorylated SMAD1/5/8. Conditional mutation of BMP type I receptors in interneuron precursors significantly reduces the number of cortical PV(+) interneurons in the adult brain. Thus, BMP4 signaling through type I receptors regulates the differentiation of two major medial ganglionic eminence-derived interneuron populations and defines their relative numbers in the cortex.
  Development 09/2009; 136(15):2633-42.
• Article: Shape meets polarity in Japan.

  Bob Goldstein, Hiroshi Hamada
  [show abstract] [hide abstract]
  ABSTRACT: A diverse group of developmental biologists who study cell polarity gathered in late March 2009 at the RIKEN Center for Developmental Biology in Kobe, Japan, for a symposium entitled ;Shape and Polarity'. The organizers, Masatoshi Takeichi, Fumio Matsuzaki, Hitoshi Sawa [RIKEN Center for Developmental Biology (CDB), Kobe, Japan] and Carl-Philipp Heisenberg (Max Planck Institute, Dresden, Germany), put together an engaging program that highlighted recent progress towards understanding the mechanisms of cell polarization during development, and the functions of cell polarity in shaping development.
  Development 09/2009; 136(15):2487-92.
• Article: Functional and phylogenetic analysis shows that Fgf8 is a marker of genital induction in mammals but is not required for external genital development.

  Ashley W Seifert, Terry Yamaguchi, Martin J Cohn
  [show abstract] [hide abstract]
  ABSTRACT: In mammalian embryos, male and female external genitalia develop from the genital tubercle. Outgrowth of the genital tubercle is maintained by the urethral epithelium, and it has been reported that Fgf8 mediates this activity. To test directly whether Fgf8 is required for external genital development, we conditionally removed Fgf8 from the cloacal/urethral epithelium. Surprisingly, Fgf8 is not necessary for initiation, outgrowth or normal patterning of the external genitalia. In early genital tubercles, we found no redundant Fgf expression in the urethral epithelium, which contrasts with the situation in the apical ectodermal ridge (AER) of the limb. Analysis of Fgf8 pathway activity showed that four putative targets are either absent from early genital tubercles or are not regulated by Fgf8. We therefore examined the distribution of Fgf8 protein and report that, although it is present in the AER, Fgf8 is undetectable in the genital tubercle. Thus, Fgf8 is transcribed, but the signaling pathway is not activated during normal genital development. A phylogenetic survey of amniotes revealed Fgf8 expression in genital tubercles of eutherian and metatherian mammals, but not turtles or alligators, indicating that Fgf8 expression is neither a required nor a conserved feature of amniote external genital development. The results indicate that Fgf8 expression is an early readout of the genital initiation signal rather than the signal itself. We propose that induction of external genitalia involves an epithelial-epithelial interaction at the cloacal membrane, and suggest that the cloacal ectoderm may be the source of the genital initiation signal.
  Development 09/2009; 136(15):2643-51.
• Article: Cx30.2 enhancer analysis identifies Gata4 as a novel regulator of atrioventricular delay.

  Nikhil V Munshi, John McAnally, Svetlana Bezprozvannaya, Jeff M Berry, James A Richardson, Joseph A Hill, Eric N Olson
  [show abstract] [hide abstract]
  ABSTRACT: The cardiac conduction system comprises a specialized tract of electrically coupled cardiomyocytes responsible for impulse propagation through the heart. Abnormalities in cardiac conduction are responsible for numerous forms of cardiac arrhythmias, but relatively little is known about the gene regulatory mechanisms that control the formation of the conduction system. We demonstrate that a distal enhancer for the connexin 30.2 (Cx30.2, also known as Gjd3) gene, which encodes a gap junction protein required for normal atrioventricular (AV) delay in mice, is necessary and sufficient to direct expression to the developing AV conduction system (AVCS). Moreover, we show that this enhancer requires Tbx5 and Gata4 for proper expression in the conduction system, and Gata4(+/-) mice have short PR intervals indicative of accelerated AV conduction. Thus, our results implicate Gata4 in conduction system function and provide a clearer understanding of the transcriptional pathways that impact normal AV delay.
  Development 09/2009; 136(15):2665-74.
• Article: Nkx6-1 controls the identity and fate of red nucleus and oculomotor neurons in the mouse midbrain.

  Nilima Prakash, Eduardo Puelles, Kristine Freude, Dietrich Trümbach, Daniela Omodei, Michela Di Salvio, Lori Sussel, Johan Ericson, Maike Sander, Antonio Simeone, Wolfgang Wurst
  [show abstract] [hide abstract]
  ABSTRACT: Little is known about the cues controlling the generation of motoneuron populations in the mammalian ventral midbrain. We show that Otx2 provides the crucial anterior-posterior positional information for the generation of red nucleus neurons in the murine midbrain. Moreover, the homeodomain transcription factor Nkx6-1 controls the proper development of the red nucleus and of the oculomotor and trochlear nucleus neurons. Nkx6-1 is expressed in ventral midbrain progenitors and acts as a fate determinant of the Brn3a(+) (also known as Pou4f1) red nucleus neurons. These progenitors are partially dorsalized in the absence of Nkx6-1, and a fraction of their postmitotic offspring adopts an alternative cell fate, as revealed by the activation of Dbx1 and Otx2 in these cells. Nkx6-1 is also expressed in postmitotic Isl1(+) oculomotor and trochlear neurons. Similar to hindbrain visceral (branchio-) motoneurons, Nkx6-1 controls the proper migration and axon outgrowth of these neurons by regulating the expression of at least three axon guidance/neuronal migration molecules. Based on these findings, we provide additional evidence that the developmental mechanism of the oculomotor and trochlear neurons exhibits more similarity with that of special visceral motoneurons than with that controlling the generation of somatic motoneurons located in the murine caudal hindbrain and spinal cord.
  Development 09/2009; 136(15):2545-55.
• Article: Lighting up mRNA localization in Drosophila oogenesis.

  Agata N Becalska, Elizabeth R Gavis
  [show abstract] [hide abstract]
  ABSTRACT: The asymmetric localization of four maternal mRNAs - gurken, bicoid, oskar and nanos - in the Drosophila oocyte is essential for the development of the embryonic body axes. Fluorescent imaging methods are now being used to visualize these mRNAs in living tissue, allowing dynamic analysis of their behaviors throughout the process of localization. This review summarizes recent findings from such studies that provide new insight into the elaborate cellular mechanisms that are used to transport mRNAs to different regions of the oocyte and to maintain their localized distributions during oogenesis.
  Development 09/2009; 136(15):2493-503.
• Article: Regulation of cell surface protease matriptase by HAI2 is essential for placental development, neural tube closure and embryonic survival in mice.

  Roman Szabo, John P Hobson, Kristina Christoph, Peter Kosa, Karin List, Thomas H Bugge
  [show abstract] [hide abstract]
  ABSTRACT: Hypomorphic mutations in the human SPINT2 gene cause a broad spectrum of abnormalities in organogenesis, including organ and digit duplications, atresia, fistulas, hypertelorism, cleft palate and hamartoma. SPINT2 encodes the transmembrane serine protease inhibitor HAI2 (placental bikunin), and the severe developmental effects of decreased HAI2 activity can be hypothesized to be a consequence of excess pericellular proteolytic activity. Indeed, we show here that HAI2 is a potent regulator of protease-guided cellular responses, including motogenic activity and transepithelial resistance of epithelial monolayers. Furthermore, we show that inhibition of the transmembrane serine protease matriptase (encoded by St14) is an essential function of HAI2 during tissue morphogenesis. Genetic inactivation of the mouse Spint2 gene led to defects in neural tube closure, abnormal placental labyrinth development associated with loss of epithelial cell polarity, and embryonic demise. Developmental defects observed in HAI2-deficient mice were caused by unregulated matriptase activity, as both placental development and embryonic survival in HAI2-deficient embryos were completely restored by the simultaneous genetic inactivation of matriptase. However, neural tube defects were detected in HAI2-deficient mice even in the absence of matriptase, although at lower frequency, indicating that the inhibition of additional serine protease(s) by HAI2 is required to complete neural development. Finally, by genetic complementation analysis, we uncovered a unique and complex functional interaction between HAI2 and the related HAI1 in the regulation of matriptase activity during development. This study indicates that unregulated matriptase-dependent cell surface proteolysis can cause a diverse array of abnormalities in mammalian development.
  Development 09/2009; 136(15):2653-63.
• Article: Axons find their way in the snow.

  Yimin Zou
  [show abstract] [hide abstract]
  ABSTRACT: In February 2009, Keystone, Colorado, hosted the third Symposium on; Axonal Connections: Molecular Cues for Development and Regeneration', organized by Marie Filbin, John Flanagan and Liqun Luo. Researchers from diverse backgrounds spent the week discussing the latest findings in axon guidance, synapse formation, dendrite development and axon regeneration. The meeting was held jointly with another Keystone Symposium on ;Neurodegenerative Diseases: New Molecular Mechanisms', and the two meetings profited from the lively discussions fuelled with questions from both fields in the joint sessions, which featured topics of common interest, such as axon degeneration, regeneration and neural stem cells.
  Development 08/2009; 136(13):2135-9.
• Article: Cell volume regulation is initiated in mouse oocytes after ovulation.

  Alina P Tartia, Nirmala Rudraraju, Tiffany Richards, Mary-Anne Hammer, Prudence Talbot, Jay M Baltz
  [show abstract] [hide abstract]
  ABSTRACT: Fertilized mouse eggs regulate their size principally by accumulating glycine as an intracellular osmolyte using the GLYT1 (SLC6A9) transporter, a mechanism of cell volume homeostasis apparently unique to early embryos before the morula stage. However, nothing was known of cell volume regulation in oocytes before fertilization. We show here that GLYT1 is quiescent in mouse germinal-vesicle-stage oocytes but becomes fully activated within hours after ovulation is triggered. This initiates accumulation of substantial amounts of intracellular glycine in oocytes during meiotic progression, reaching a maximal level in mature eggs. Measurements of endogenous free glycine showed that there were nearly undetectable levels in ovarian germinal-vesicle-stage oocytes, but high levels were present in mature ovulated eggs and in preimplantation embryos through the two-cell stage, but not in morulae. Furthermore, intracellular glycine was regulated in response to changes in external tonicity in eggs and embryos through the two-cell stage, but not in oocytes or embryos after the two-cell stage. Before activation of GLYT1, oocytes were unable to independently regulate their volume. As GLYT1 became active, however, oocyte volume decreased substantially and oocytes gained the ability to regulate their size, which required GLYT1 activity. Before ovulation, oocyte size was instead determined by a strong adhesion to the rigid extracellular matrix of the oocyte, the zona pellucida, which was released coincident with GLYT1 activation. The ability to acutely regulate cell size is thus acquired by the oocyte only after ovulation, when it first develops glycine-dependent cell volume regulation.
  Development 08/2009; 136(13):2247-54.
• Article: Cux2 functions downstream of Notch signaling to regulate dorsal interneuron formation in the spinal cord.

  Angelo Iulianella, Madhulika Sharma, Greg B Vanden Heuvel, Paul A Trainor
  [show abstract] [hide abstract]
  ABSTRACT: Obtaining the diversity of interneuron subtypes in their appropriate numbers requires the orchestrated integration of progenitor proliferation with the regulation of differentiation. Here we demonstrate through loss-of-function studies in mice that the Cut homeodomain transcription factor Cux2 (Cutl2) plays an important role in regulating the formation of dorsal spinal cord interneurons. Furthermore, we show that Notch regulates Cux2 expression. Although Notch signaling can be inhibitory to the expression of proneural genes, it is also required for interneuron formation during spinal cord development. Our findings suggest that Cux2 might mediate some of the effects of Notch signaling on interneuron formation. Together with the requirement for Cux2 in cell cycle progression, our work highlights the mechanistic complexity in balancing neural progenitor maintenance and differentiation during spinal cord neurogenesis.
  Development 08/2009; 136(14):2329-34.
• Article: The RNA-binding protein Mex3b has a fine-tuning system for mRNA regulation in early Xenopus development.

  Hitomi Takada, Takahiro Kawana, Yuzuru Ito, Reiko F Kikuno, Hiroshi Mamada, Toshiyuki Araki, Hisashi Koga, Makoto Asashima, Masanori Taira
  [show abstract] [hide abstract]
  ABSTRACT: Post-transcriptional control by RNA-binding proteins is a precise way to assure appropriate levels of gene expression. Here, we identify a novel mRNA regulatory system involving Mex3b (RKHD3) and demonstrate its role in FGF signaling. mex3b mRNA has a 3' long conserved UTR, named 3'LCU, which contains multiple elements for both mRNA destabilization and translational enhancement. Notably, Mex3b promotes destabilization of its own mRNA by binding to the 3'LCU, thereby forming a negative autoregulatory loop. The combination of positive regulation and negative autoregulation constitutes a fine-tuning system for post-transcriptional control. In early embryogenesis, Mex3b is involved in anteroposterior patterning of the neural plate. Consistent with this, Mex3b can attenuate FGF signaling and destabilize mRNAs for the FGF signaling components Syndecan 2 and Ets1b through their 3' UTRs. These data suggest that the 3'LCU-mediated fine-tuning system determines the appropriate level of mex3b expression, which in turn contributes to neural patterning through regulating FGF signaling.
  Development 08/2009; 136(14):2413-22.
• Article: C. elegans Rab GTPase activating protein TBC-2 promotes cell corpse degradation by regulating the small GTPase RAB-5.

  Weida Li, Wei Zou, Dongfeng Zhao, Jiacong Yan, Zuoyan Zhu, Jing Lu, Xiaochen Wang
  [show abstract] [hide abstract]
  ABSTRACT: During apoptosis, dying cells are quickly internalized by neighboring cells or phagocytes, and are enclosed in phagosomes that undergo a maturation process to generate the phagoslysosome, in which cell corpses are eventually degraded. It is not well understood how apoptotic cell degradation is regulated. Here we report the identification and characterization of the C. elegans tbc-2 gene, which is required for the efficient degradation of cell corpses. tbc-2 encodes a Rab GTPase activating protein (GAP) and its loss of function affects several events of phagosome maturation, including RAB-5 release, phosphatidylinositol 3-phosphate dynamics, phagosomal acidification, RAB-7 recruitment and lysosome incorporation, which leads to many persistent cell corpses at various developmental stages. Intriguingly, the persistent cell corpse phenotype of tbc-2 mutants can be suppressed by reducing gene expression of rab-5, and overexpression of a GTP-locked RAB-5 caused similar defects in phagosome maturation and cell corpse degradation. We propose that TBC-2 functions as a GAP to cycle RAB-5 from an active GTP-bound to an inactive GDP-bound state, which is required for maintaining RAB-5 dynamics on phagosomes and serves as a switch for the progression of phagosome maturation.
  Development 08/2009; 136(14):2445-55.
• Article: Somatic cAMP signaling regulates MSP-dependent oocyte growth and meiotic maturation in C. elegans.

  J Amaranath Govindan, Saravanapriah Nadarajan, Seongseop Kim, Todd A Starich, David Greenstein
  [show abstract] [hide abstract]
  ABSTRACT: Soma-germline interactions control fertility at many levels, including stem cell proliferation, meiosis and gametogenesis, yet the nature of these fundamental signaling mechanisms and their potential evolutionary conservation are incompletely understood. In C. elegans, a sperm-sensing mechanism regulates oocyte meiotic maturation and ovulation, tightly coordinating sperm availability and fertilization. Sperm release the major sperm protein (MSP) signal to trigger meiotic resumption (meiotic maturation) and to promote contraction of the follicle-like gonadal sheath cells that surround oocytes. Using genetic mosaic analysis, we show that all known MSP-dependent meiotic maturation events in the germline require Galpha(s)-adenylate cyclase signaling in the gonadal sheath cells. We show that the MSP hormone promotes the sustained actomyosin-dependent cytoplasmic streaming that drives oocyte growth. Furthermore, we demonstrate that efficient oocyte production and cytoplasmic streaming require Galpha(s)-adenylate cyclase signaling in the gonadal sheath cells, thereby providing a somatic mechanism that coordinates oocyte growth and meiotic maturation with sperm availability. We present genetic evidence that MSP and Galpha(s)-adenylate cyclase signaling regulate oocyte growth and meiotic maturation in part by antagonizing gap-junctional communication between sheath cells and oocytes. In the absence of MSP or Galpha(s)-adenylate cyclase signaling, MSP binding sites are enriched and appear clustered on sheath cells. We discuss these results in the context of a model in which the sheath cells function as the major initial sensor of MSP, potentially via multiple classes of G-protein-coupled receptors. Our findings highlight a remarkable similarity between the regulation of meiotic resumption by soma-germline interactions in C. elegans and mammals.
  Development 08/2009; 136(13):2211-21.