The receptor tyrosine phosphatase Lar regulates adhesion between <i>Drosophila</i> male germline stem cells and the niche

Srinivasan, Shrividhya; Mahowald, Anthony P.; Fuller, Margaret T.

doi:10.1242/dev.070052

Cited by 25 publications

(20 citation statements)

References 82 publications

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“…Most known roles of LAR have been shown to be or are presumed to be cell autonomous (for examples, see Srinivasan et al 2012;Wang et al 2012). Our studies indicate that PTP-3B can act autonomously in the Q cells, possibly as a receptor.…”

Section: Ptp-3/lar Controls Q Migrationmentioning

confidence: 58%

“…The ptp-3 locus encodes a family of transmembrane molecules characterized by extracellular immunoglobulin and fibronectin type III repeats and two intracellular phosphatase domains. PTP-3/LAR-related molecules are involved in multiple aspects of nervous system development, including axon guidance, neurite development, and synaptic organization (Ackley et al 2005;Johnson et al 2006;Pawson et al 2008;Hofmeyer and Treisman 2009;Wang et al 2012), cell movements in gastrulation (Harrington et al 2002), and germline stem cell maintenance (Srinivasan et al 2012).…”

mentioning

confidence: 99%

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Transmembrane Proteins UNC-40/DCC, PTP-3/LAR, and MIG-21 Control Anterior–Posterior Neuroblast Migration with Left–Right Functional Asymmetry in Caenorhabditis elegans

2012

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Migration of neurons and neural crest cells is of central importance to the development of nervous systems. In Caenorhabditis elegans, the QL neuroblast on the left migrates posteriorly, and QR on the right migrates anteriorly, despite similar lineages and birth positions with regard to the left-right axis. Initial migration is independent of a Wnt signal that controls later anteriorposterior Q descendant migration. Previous studies showed that the transmembrane proteins UNC-40/DCC and MIG-21, a novel thrombospondin type I repeat containing protein, act redundantly in left-side QL posterior migration. Here we show that the LAR receptor protein tyrosine phosphatase PTP-3 acts with MIG-21 in parallel to UNC-40 in QL posterior migration. We also show that in right-side QR, the UNC-40 and PTP-3/MIG-21 pathways mutually inhibit each other's role in posterior migration, allowing anterior QR migration. Finally, we present evidence that these proteins act autonomously in the Q neuroblasts. These studies indicate an inherent left-right asymmetry in the Q neuroblasts with regard to UNC-40, PTP-3, and MIG-21 function that results in posterior vs. anterior migration.C ELL migration is a fundamental event in the development of nervous systems. In the vertebrate central nervous system, neurons and neuroblasts migrate radially to populate distinct layers in the cerebellar and cerebral cortices, and neural crest cells migrate along distinct paths in the vertebrate embryo to give rise to the peripheral nervous system. The Q neuroblasts in Caenorhabditis elegans are a useful model to study the migration of neuroblasts and neurons in the anterior-posterior axis. The Q neuroblasts are a bilaterally symmetric pair of cells in the posteriorlateral region of the animal, with QR on the right side and QL on the left side (Sulston and Horvitz 1977). The Q neuroblasts are born in embryogenesis and are the sisters of the V5 hypodermal seam cells. By 5 hr after hatching, QR has migrated anteriorly and divided over the V4 seam cell, and QL has migrated posteriorly and divided over the V5 seam cell (Honigberg and Kenyon 2000;Chapman et al. 2008;Dyer et al. 2010). The resulting Q cell descendants then undergo a pattern of migration, division, and programmed cell death resulting in three neurons each (AQR, SDQR, and AVM on the right from QR; and PQR, SDQL, and PVM on the left from QL) (Sulston and Horvitz 1977;Chalfie and Sulston 1981). The QR descendant AQR migrates the longest distance to a region near the anterior deirid ganglion in the head, and the QL descendant PQR migrates the longest distance posteriorly to the phasmid ganglion in the tail (Sulston and Horvitz 1977;White et al. 1986;Chapman et al. 2008). The posterior migration of QL descendants requires the activity of the MAB-5/Hox transcription factor, expression of which is induced in QL descendants by an EGL-20/Wnt signal emanating from the posterior (Chalfie et al.

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Section: Ptp-3/lar Controls Q Migrationmentioning

confidence: 58%

mentioning

confidence: 99%

Transmembrane Proteins UNC-40/DCC, PTP-3/LAR, and MIG-21 Control Anterior–Posterior Neuroblast Migration with Left–Right Functional Asymmetry in Caenorhabditis elegans

2012

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“…In the Drosophila testis, Rap-GEF/Rap signaling controls the accumulation of E-cadherin at the GSC-niche junction, thereby anchoring GSCs to the niche . Recently, the transmembrane receptor tyrosine phosphatase Leukocyte-antigenrelated-like (Lar) has also been shown to be required in GSCs for maintaining E-cadherin accumulation between GSCs and their niche in the Drosophila testis (Srinivasan et al, 2012). It is likely that on-going genetic studies in the Drosophila stem cell systems will identify more regulators of stem cell-niche adhesion.…”

Section: Stem Cell-niche Adhesion Is Regulated By Stem Cell-intrinsicmentioning

confidence: 99%

Adhesion in the stem cell niche: biological roles and regulation

2013

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Stem cell self-renewal is tightly controlled by the concerted action of stem cell-intrinsic factors and signals within the niche. Niche signals often function within a short range, allowing cells in the niche to self-renew while their daughters outside the niche differentiate. Thus, in order for stem cells to continuously self-renew, they are often anchored in the niche via adhesion molecules. In addition to niche anchoring, however, recent studies have revealed other important roles for adhesion molecules in the regulation of stem cell function, and it is clear that stem cell-niche adhesion is crucial for stem cell self-renewal and is dynamically regulated. Here, we highlight recent progress in understanding adhesion between stem cells and their niche and how this adhesion is regulated.

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“…In addition, PTEN, LKB1 and AMPK are found to regulate PGC proliferation is this species (Narbonne and Roy, 2006). Increasing information is becoming available that the supportive cells in the niche are also required to allow maturation of the stem cells to happen (Srinivasan et al, 2012). In other words, a subtle balance between inducing and inhibiting factors seems to determine the cell fate.…”

Section: Drosophila (D) Melanogastermentioning

confidence: 99%

Development of malignant germ cells - the genvironmental hypothesis

Looijenga¹,

Agthoven²,

Biermann³

2013

Int. J. Dev. Biol.

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Human germ cell tumors are of interest because of their epidemiology, clinic and pathobiology. Histologically, they are subdivided into various elements, with similarities to embryogenesis. Recent insight triggered development of a higher order division into five types of human germ cell tumors. In the context of male germ cells, only three are relevant; Type I: teratomas and yolk sac tumors of neonates and infants; Type II: seminomas and nonseminomas of (predominantly) adolescents and adults; and Type III: spermatocytic seminomas of the elderly. Various animal models, both occurring spontaneous or induced, are reported, of which their relevance is still a matter of debate. Recent multidisciplinary studies have led to a significant increase in our understanding of the parameters involved in the earliest pathogenetic steps of human germ cells tumors, particularly the seminomas and nonseminomas (Type II). This paper will discuss a number of interesting insights into the normal and aberrant regulation of germ cell development, resulting in the so-called genvironmental hypothesis. This assumes a subtle interaction between environmental-and (epi)genetic parameters, resulting in clinical/phenotypical characteristics. These influence signaling pathways and thereby developmental processes, including gonadal development, germ cell proliferation, maturation and apoptosis. In the case of a disturbed physiology, either due to the germ cell itself, or the micro-environment, embryonic germ cells, during a specific window of sensitization, might be blocked in their maturation, resulting in carcinoma in situ or gonadoblastoma, the precursors of seminomas and nonseminomas. The level of testicularization of the gonad determines the histological composition of the precursor. These insights will allow a better definition of individuals at risk of developing a germ cell malignancy, and allow a better selection of scientific approaches to elucidate the corresponding pathogenesis.

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The receptor tyrosine phosphatase Lar regulates adhesion between Drosophila male germline stem cells and the niche

Cited by 25 publications

References 82 publications

Transmembrane Proteins UNC-40/DCC, PTP-3/LAR, and MIG-21 Control Anterior–Posterior Neuroblast Migration with Left–Right Functional Asymmetry in Caenorhabditis elegans

Transmembrane Proteins UNC-40/DCC, PTP-3/LAR, and MIG-21 Control Anterior–Posterior Neuroblast Migration with Left–Right Functional Asymmetry in Caenorhabditis elegans

Adhesion in the stem cell niche: biological roles and regulation

Development of malignant germ cells - the genvironmental hypothesis

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