Neuronal Migrations and Axon Fasciculation Are Disrupted in ina-1 Integrin Mutants

Baum, Paul; Garriga, Gian

doi:10.1016/s0896-6273(00)80347-5

Cited by 168 publications

(186 citation statements)

References 59 publications

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“…This defect is observed in certain ina-1 alleles and other mutants that affect cell migration (Baum and Garriga 1997). One mutant, mw105, showed significantly aberrant DTC migration with a highly penetrant migration defect (99.5%, n = 400) visible as coiled-up gonad arms (Fig.…”

Section: Resultsmentioning

confidence: 90%

“…A weak nonlethal allele of ina-1 causes dorsal migration defects (Baum and Garriga 1997). Similar gonad defects were observed with DTC-specific expression of a dominantnegative pat-3 transgene, with a PAT-3 cytoplasmic tail mutant, or by pat-3 RNA interference (RNAi) (Lee et al 2001(Lee et al , 2005.…”

mentioning

confidence: 68%

“…In wild-type N2 nematodes, ina-1 is expressed in migrating neurons, the pharynx, and the DTCs, but not in body-wall muscles (Baum and Garriga 1997). INA-1ϻGFP was present in the DTCs at the L2 stage prior to migration and maintained throughout L4 …”

Section: Resultsmentioning

confidence: 96%

“…Executing the DTC migratory program requires the coordinated action of matrix metalloproteases, the netrin signaling system, plus integrins and other signaling molecules that regulate the cytoskeleton (Hubbard and Greenstein 2000;Cram et al 2006). Molecular regulation of gonad size and the signals that stop DTC migration are not known.The integrin heterodimer composed of INA-1/␣ and PAT-3/␤ is expressed by the DTC throughout migration (Gettner et al 1995;Baum and Garriga 1997). A weak nonlethal allele of ina-1 causes dorsal migration defects (Baum and Garriga 1997).…”

mentioning

confidence: 99%

“…The integrin heterodimer composed of INA-1/␣ and PAT-3/␤ is expressed by the DTC throughout migration (Gettner et al 1995;Baum and Garriga 1997). A weak nonlethal allele of ina-1 causes dorsal migration defects (Baum and Garriga 1997).…”

mentioning

confidence: 99%

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Control ofC. eleganshermaphrodite gonad size and shape byvab-3/Pax6-mediated regulation of integrin receptors

Meighan¹,

Schwarzbauer²

2007

Genes Dev.

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Integrin receptors for extracellular matrix are critical for cell motility, but the signals that determine when to stop are not known. Analysis of distal tip cell (DTC) migration during gonadogenesis in Caenorhabditis elegans has revealed the importance of transcription factor vab-3/Pax6 in regulating the ␣ integrin genes, ina-1 and pat-2. Utilizing vab-3 mutants, we show that the downregulation of ina-1 is necessary for DTC migration cessation and the up-regulation of pat-2 is required for directionality. These results demonstrate concomitant, but distinct roles in migration for each integrin. Notably, transcriptional control of migration termination provides a new mechanism for regulation of morphogenesis and organ size.Supplemental material is available at http://www.genesdev.org.Received January 24, 2007; revised version accepted May 21, 2007. Integrins are heterodimeric transmembrane receptors consisting of ␣ and ␤ subunits that link the extracellular matrix (ECM) to the actin cytoskeleton via a wide array of intracellular proteins (Hynes 2002). Through these interactions, integrins regulate cell migration, division, differentiation, and adhesion. Coordinated regulation of integrin adhesive strength over space and time determines the speed and directionality of cell migration in vitro (Palecek et al. 1997;Ridley et al. 2003), and abnormal cell migration has been linked to certain developmental defects caused by loss of integrins in vivo (Bouvard et al. 2001). However, detailed in vivo analyses of integrins in migration are complicated by embryonic lethality of integrin-null mutants and by pleiotropic, redundant, or overlapping functions among the 18 ␣ and eight ␤ chains in mammals. Some of the experimental constraints inherent in studies on mice can be bypassed by using the nematode Caenorhabditis elegans, which has two conserved integrin receptors composed of an ina-1/␣ or pat-2/␣ subunit associated with the pat-3/␤ integrin subunit (Cox et al. 2004).Post-embryonic gonadogenesis in C. elegans provides an excellent model of cell migration during development. The shape of the hermaphrodite gonad is dictated by migration of two leader cells called the distal tip cells (DTCs) (Hubbard and Greenstein 2000). The DTCs begin to migrate away from the gonad primordium on the ventral ECM of the nematode in larval stage L2 (Fig. 1A). During the third larval stage, they turn and migrate to the dorsal side, followed by a second turn and migration toward the mid-body of the nematode throughout the L4 stage. Migration ends on the dorsal surface approximately opposite the vulva, resulting in two U-shaped gonad arms coincident with the onset of adulthood (Fig. 1A,B). Executing the DTC migratory program requires the coordinated action of matrix metalloproteases, the netrin signaling system, plus integrins and other signaling molecules that regulate the cytoskeleton (Hubbard and Greenstein 2000;Cram et al. 2006). Molecular regulation of gonad size and the signals that stop DTC migration are not known.The integrin heterod...

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Section: Resultsmentioning

confidence: 90%

mentioning

confidence: 68%

Section: Resultsmentioning

confidence: 96%

mentioning

confidence: 99%

mentioning

confidence: 99%

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Control ofC. eleganshermaphrodite gonad size and shape byvab-3/Pax6-mediated regulation of integrin receptors

Meighan¹,

Schwarzbauer²

2007

Genes Dev.

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TheCaenorhabditis elegans gonad: A test tube for cell and developmental biology

2000

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Sexual reproduction of multicellular organisms depends critically on the coordinate development of the germ line and somatic gonad, a process known as gonadogenesis. Together these tissues ensure the formation of functional gametes and, in the female of many species, create a context for production and further development of the zygote. Since the future of the species hangs in the balance, it is not surprising that gonadogenesis is a complex process involving conserved and multi-faceted developmental mechanisms. Genetic, anatomical, cell biological, and molecular experiments have established the nematode Caenorhabditis elegans as a paradigm for studying gonadogenesis. Furthermore, these studies demonstrate the utility of C. elegans gonadogenesis for exploring broad issues in cell and developmental biology, such as cell fate specification, morphogenesis, cell signaling, cell cycle control, and programmed cell death. The synergy of molecular genetics and cell biology conducted at single-cell resolution in real time permits an extraordinary depth of analysis in this organism. In this review, we first describe the embryonic and post-embryonic development and morphology of the C. elegans gonad. Next we recount seminal experiments that established the field, highlight recent results that provide insight into conserved developmental mechanisms, and present future prospects for the field.

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A pair as a minimum: The two fibroblast growth factors of the nematode Caenorhabditis elegans

Birnbaum

Popovici

Roubin

2004

Developmental Dynamics

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Neuronal Migrations and Axon Fasciculation Are Disrupted in ina-1 Integrin Mutants

Cited by 168 publications

References 59 publications

Control ofC. eleganshermaphrodite gonad size and shape byvab-3/Pax6-mediated regulation of integrin receptors

Control ofC. eleganshermaphrodite gonad size and shape byvab-3/Pax6-mediated regulation of integrin receptors

TheCaenorhabditis elegans gonad: A test tube for cell and developmental biology

A pair as a minimum: The two fibroblast growth factors of the nematode Caenorhabditis elegans

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