Daedalus: Vacuum in miniature

blasts in the LPM with a fluorescent tag andmonitoring their fate. This appeared to bepredetermined: all the progeny of a givenangioblast ended up in either the aorta or avein, but not both. Zhong et al. then looked atwhether gridlock prompts angioblasts to formarteries. They decreased levels of the Gridlockprotein by using modified antisense oligo-nucleotides, and found a dose-dependentreduction in the size of the aorta, and anincrease in the adjacent vein. Reciprocally,increasing Gridlock activity by injecting grid-lock messenger RNA into early embryosdecreased the size of the vein (though it did notincrease the size of the aorta). The implica-tion is that angioblasts make up a limited poolof precursors whose default fate is venous,and that the expression of gridlock suppressesthe venous characteristics and helps to drivethe precursors towards forming an aorta.

Transcriptional repressors that are relatedto Gridlock can be expressed in response tosignals from the Notch family of receptorproteins. To find out whether this applies toGridlock as well, Zhong et al. injected eitheran activated form of Notch1 or an inhibitor ofthe Notch1 signalling pathway into zebrafishembryos. They found that activation of thepathway by Notch1 induced the expression of gridlock, whereas suppression of the path-way both reduced gridlock expression anddisrupted the formation of the aorta.

Another study5, by Lawson et al., hadalready implicated the Notch pathway inarterial fate, particularly in the expression of artery-specific proteins such as ephrinB2. But these authors found that certain arterialcharacteristics — such as the expression ofephrinB2 — could be ablated even when gridlock expression was maintained, raising questions about where gridlock comes intoartery determination. These findings can bereconciled with those of Zhong et al. if oneassumes that the response to gridlock is dosedependent, as indeed Zhong et al.’s results suggest. So, the total absence of gridlock

results in the default venous fate and oblitera-tion of the aorta. Partial expression of gridlock(as may have occurred in Lawson et al.’s study)allows some characteristics of an artery todevelop, but not all, as reflected by the lack of expression of proteins such as ephrinB2.

It seems, then, that the Notch/Gridlockpathway predetermines the fate of angioblasts(Fig. 1). Of course, questions remain. How,for example, do these precursors migrate tothe appropriate site and then coalesce onlywith similarly fated cells? The ephrin proteinsand their receptors are known to be involvedin the migration and sorting of other celltypes, and seem likely to help maintain theidentities of different blood-vessel precursors.But do they act in the LPM, in the migrationpathway, or in blood vessels themselves?

Moreover, although the nature of vascu-lar cells may indeed be predetermined by a genetic programme before blood flowbegins, many studies of vessel transplanta-tion in embryos and adults have indicatedthat vessels can remodel and switch theiridentity. Indeed, surgeons commonly trans-plant the saphenous vein into segments ofdiseased arteries. It will be fascinating to look at the involvement of proteins such asNotch1 and Gridlock during cellular repro-gramming in the course of arterial diseaseand in transplanted veins. With this in mind,we now need to find out if the zebrafish workcan be translated to mammals. Stay tuned for further gridlock alerts! ■

Gavin Thurston and George D. Yancopoulos are atRegeneron Pharmaceuticals, Inc., 777 Old Saw MillRiver Road, Tarrytown, New York 10591, USA.e-mails: gavin.thurston@regeneron.comgeorge@regeneron.com1. Zhong, T. P., Childs, S., Leu, J. P. & Fishman, M. C. Nature 414,

216–220 (2001).2. Wang, H. U., Chen, Z. F. & Anderson, D. J. Cell 93, 741–753

(1998).3. Weinstein, B. M., Stemple, D. L., Driever, W. & Fishman, M. C.

Nature Med. 1, 1143–1147 (1995).4. Zhong, T. P., Rosenberg, M., Mohideen, M. A., Weinstein, B. &

Fishman, M. C. Science 287, 1820–1824 (2000).5. Lawson, N. D. et al. Development 128, 3675–3683 (2001).

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164 NATURE | VOL 414 | 8 NOVEMBER 2001 | www.nature.com

Daedalus

Vacuum in miniatureMeredith Thring once proposed adomestic robot to operate other machines,such as the vacuum cleaner, but wasunable to give it human intelligence.Annoyed by the vacuum cleaner, Daedalusis now scaling it down. His ideal is adedicated, chip-operated cleaner maybeonly 3 cm across. Unlike bigger machines,it will need no operator, and will runcontinuously, like a diminutive pet. Ontiny wheels it will nose along the carpet,sucking vigorously at everything thatseems foreign to its environment. It willpack loose dust, skin particles and fibreinto a little sack.

Like W. Grey Walter’s old Machinahabilis, the new microcleaner will be alertto the state of charge of its batteries. Whenthey are low, or when its sack is full, it willhead back to an illuminated or otherwisedesignated charging base. There themicrocleaner will acquire electricity anddump its haul of rubbish, ideally in a boxthat can be disposed of when full.

A small vacuum device can be far moreeffective than a larger version, and canstudy possible waste more carefully.Modern chips allow a microcleaner to bequite flexible in its approach. An ultrasonicsensor will tell it where it is at all times. Itwill map an entire room into paralleltranches — several hundred tracks andmany hundred of metres to be covered atmaybe a metre every few minutes, perhapsat night if it is quiet enough. It will avoidcats, papers, feet and so on, rememberingto revisit the site later. It will soon learn theregular occupants of the room (such as thefurniture) and their degree of permanence.

The microcleaner should effortlesslydisplace bigger and clumsier machines. It will run all the time, cleaning an entireroom in about a week, far more efficientlythan any hand-held device. Then it willstart again. Its owner will merely have todispose of the dust and fluff it piles up atits charging-station. Unlike traditionalmachines it will need no operator, and it will tirelessly revisit sites temporarilydenied to it.

Each room or pair of rooms will haveits own cleaner. A household kitchen ordining-room will have a model thatspecializes in various sorts of spilt food; afactory will have one that knows how bestto remove the particular swarf or waste itwill find. The discriminating microcleanerwill remove green fluff from a red carpet,but not from a mixed one. But mud, loosefluff, superfluous food, loose tea-leavesand metal turnings will be removedwherever they are. David Jones

Figure 1 How blood vessels develop. a, Arteries and veins are formed from precursor cells calledangioblasts, which are initially found in the lateral posterior mesoderm (a tissue in the periphery ofthe embryo). Zhong et al.1 show that, in zebrafish, angioblasts that express the proteins Notch andGridlock will contribute to arteries. Those that do not express these proteins will contribute to veins.b, Once committed to forming arteries or veins, the cells migrate towards the midline and coalesce toform the appropriate blood vessel. The figure shows a cross-section of an embryo.

Angioblast

Low Notch and Gridlock

Venous fate

Arterial fate

EphrinB2

EphB4

Lateral posterior mesoderm

Gut

Aorta

Cardinalvein

Notochord

Neuraltube

a b

Default pathway?

High Notch and Gridlock

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