- Email: [email protected]
Drosophila Neuroscience: Should I Land or Should I Jump?
Current Biology
Dispatches Drosophila Neuroscience: Should I Land or Should I Jump? €dele*, Martha Rimniceanu, and Mark A. Frye Carola Sta Department of Integrative Biology and Physiology, University of California, Los Angeles, CA 90095, USA *Correspondence: [email protected] https://doi.org/10.1016/j.cub.2019.08.039
Information about behavioral states can be integrated in decision-making circuits. In Drosophila, the behavioral state — flying versus not flying — determines whether flies land or jump by dynamically coupling visual information to pre-motor descending neurons. The song ‘‘Should I Stay or Should I Go?’’ by the British punk rock pioneers The Clash is as catchy as its title is timeless. Who cannot relate to the question: Should I do this or should I do that? Every animal, regardless of how many neurons its nervous system is built of, constantly makes choices. But how do animals make choices? Decades of research have shown that the neural mechanisms that lead to decision making are complex and multifactorial. The internal physiological state, such as hunger, external environmental conditions, such as temperature, and the decision maker’s behavioral state, such as locomotion, are important factors in choosing one action over another. The decision whether to keep The Clash tuned in or change the radio station, for example, might depend intrinsically upon your mood or extrinsically upon how often the song gets played on the radio. Furthermore, sensory stimuli alone are often ambiguous if they are not put in context. You may feel the urge to sing to The Clash in the shower, but rather prefer to dance to it in a club. In situations where the sensory stimulus is ambiguous, context is often the key to make the difference between life, death, or reproductive fitness. An approaching predator, for example, can elicit a similar rapidly expanding looming pattern on the observer’s retina as an approaching conspecific. In insects, it has been shown that the decision to avoid or approach an ambiguous object can depend on context-sensitive inputs such as food odor [1], which can be confounded by visual circuits that only function properly during locomotion [2]. Thus, reactions to a single sensory stimulus are unlikely to be hard-wired. However, the neural mechanisms leading
to state-dependent action selection are still nebulous. Two recent studies [3,4] by Jan Ache and Gwyneth Card and their colleagues add to our understanding of where and how in the nervous system information about behavioral state can be integrated into the decision-making chain. In the first study [3], Ache and colleagues demonstrate how Drosophila melanogaster flies integrate behavioral state by dynamically coupling visual input to output pathways to elicit distinct behaviors. In a second study published in Current Biology, Ache and colleagues [4] investigate where in the visual processing networks the coupling to output pathways could occur. When tethered Drosophila are presented with a looming object, Ache and colleagues [3] found that an identical visual looming stimulus can trigger two categorically distinct motor programs — flying flies simultaneously extend all six legs and initiate landing reactions whereas perching flies extend the middle legs and raise their wings to initiate jumping and takeoff. Information about the behavioral state (flying versus perching) can thus be combined with visual input to select the appropriate action (landing versus takeoff) through at least two distinct motor pathways. Ache and colleagues [3] determined where in the neural processing stream the commands for landing and escape are distinguished. In adult Drosophila, 350 pairs of pre-motor ‘descending neurons’ connect the brain to the ventral nerve cord [5], which houses the motor centers that control behavior. Traditionally, descending neurons are viewed as a bottleneck [6], relaying commands from many thousands of brain neurons to only
dozens of central pattern generators in the ventral nerve cord, which then drive combinations of motor neurons to produce coordinated behaviors. The sensorimotor pathway controlling looming-evoked takeoff in Drosophila includes the fast giant-fiber descending neurons [7]. However, the neural circuit that controls landing was unknown. Ache and colleagues [3] found that only two bilaterally symmetric pairs of descending neurons (DNp07 and DNp10) evoke landing-like extension of all six legs when activated optogenetically. Interestingly, the responses to looming visual stimuli of both descending neuron types appeared only when the animals were flying. In tethered non-flying flies, supra-threshold visual responses were abolished in DNp07, while in DNp10 visual responses were strongly attenuated below the threshold required to elicit leg movements. But how exactly is the state of flight communicated to these neurons? One candidate to conditionally link the same sensory input to different behaviors in a state-dependent manner is the biogenic amine octopamine — the invertebrate analog of norepinephrine. On flight initiation, the nervous system of Drosophila is flushed with octopamine which boosts the activity of motionsensitive visual neurons [8]. To determine whether octopamine is involved in conveying flight information to descending neurons, Ache and colleagues [3] applied octopamine to the brains of non-flying Drosophila while they recorded the activity of the descending neurons. After the brain was flushed with octopamine, presenting non-flying flies with a looming stimulus resulted in a flight-like activity pattern in one of the two descending neuron types (DNp07); the
Current Biology 29, R1070–R1093, October 21, 2019 ª 2019 Published by Elsevier Ltd. R1089
Current Biology
Dispatches
State of animal
Flying
Walking/ perching
Sensory stimulus (Looming) Brain
Sensory stimulus (Looming) Brain
Sensory receptors
Sensory receptors
Sensory networks
Sensory networks
? Descending neurons A
Descending neurons B (Decoupled )
CPG A
Motor neurons A
?
Descending neurons A (Decoupled )
Descending neurons B
CPG B
CPG A
CPG B
Motor neurons B
Motor neurons A
Motor neurons B
VNC
VNC
Behavior B (Takeoff )
Behavior A (Landing)
Current Biology
Figure 1. Landing and takeoff decision pathways in Drosophila. A sensory stimulus (in this example a visual looming pattern) activates sensory receptors which then in turn activate sensory networks. The same visual stimulus can recruit several parallel sensory networks, depicted as circles. Each network might contain multiple levels of information processing (not depicted). Processed sensory information leaves the brain and is sent to parallel descending pathways (depicted in blue for landing and in green for takeoff behavior). Depending on the animal’s behavioral state (flying, left; waking/perching, right) sensory information is gated and only transmitted to one descending pathway while the other descending pathway is decoupled (doted rectangles). Question marks indicate that it remains to be tested whether the takeoff pathway in walking/perching flies is gated in a similar way as the landing pathway. Abbreviations: CPG, central pattern generator; VNC, ventral nerve cord.
other DNp10 neurons appeared to be octopamine-insensitive, but are likely to receive direct neuronal feedback from flight motor circuits. This indicates that there are at least two different pathways to relay the same sensory input to motor outputs for two different behavioral actions. Ache and colleagues [3] elegantly demonstrate that landing is not necessarily ‘commanded’ over jumping because of mutual inhibition of descending neurons [6]. Rather, the decision to land is mediated via statedependent gating (Figure 1) of
descending pathways at different sites. One gate operates through the action of octopamine to cut off presynaptic visual input before it reaches the DNp07 descending neurons, whereas the other gate acts through feedback from flight motor centers onto DNp10 themselves. It remains to be tested whether the octopamine-mediated gating takes place at the level of the visual processing networks or at the output of these networks to descending neurons. Currently the visual circuitry that transmits looming information to the landing
R1090 Current Biology 29, R1070–R1093, October 21, 2019
descending neurons is unknown. However, electron microscope reconstruction of the entire Drosophila brain is in progress [9] and it is likely that every component of this circuit will soon be identified. In their second study, Ache and colleagues [4] classify the encoding properties of potential target neurons of the octopamine-mediated gating. Using the well-characterized giant-fiber escape pathway that elicits takeoff in non-flying flies, the authors dissected the wiring logic of how salient visual features of a looming stimulus are encoded by visual projection neurons. Object recognition requires discrimination of global motion generated by self-movement from the visual features of an object. Featuredetecting visual projection neurons, such as retinal ganglion cells, have been well described in different taxa [10–12]. In Drosophila, a class of 20 distinct types of visual projection neurons, the lobula columnar (LC) neurons, are proposed to detect different visual features [13,14] and feed into distinct descending pathways [5,15]. The axon terminals of a given LC type condense into ‘optic glomeruli’ within the central brain [14,15]. A looming stimulus contains multiple salient visual features, such as the angular velocity at which the object expands or its angular size. Ache and colleagues [4] confirmed in unprecedented detail that these two features are encoded by two different LC types — LC4 encodes expansion velocity and LPLC2 encodes expansion size. Summation of both features is necessary to reach action potential threshold in the giant fibers to elicit escape responses [16,17]. Using electron microscope reconstruction, the authors further demonstrate that LC4 and LPLC2 are the sole source of direct excitatory input to these important pre-motor descending fibers. The glomeruli of two other classes of visual projection neurons, LPLC3 and LPLC4 [5], show extensive anatomical overlap with the dendrites of the two newly identified landing descending neurons [3]. It remains to be tested whether LPLC3 and LPLC4 directly synapse onto the landing descending neurons and relay information about visual features of looming patterns in a similar fashion to LC4 and LPLC2. It is intriguing, however, to hypothesize that
Current Biology
Dispatches the same type of visual information is transmitted via at least two parallel visual pathways to distinct pre-motor circuits, thereby adding another gate to the circuit. Ache and colleagues [3,4] marvelously demonstrate how multiple neural mechanisms can be combined to achieve state-dependent action selection, and provide a fly’s answer to the enduring question posed by The Clash: ‘‘Should I Stay or Should I Go?’’ REFERENCES 1. Cheng, K.Y., Colbath, R.A., and Frye, M.A. (2019). Olfactory and neuromodulatory signals reverse visual object avoidance to approach in Drosophila. Curr. Biol. 29, 2058–2065.e2. 2. Weir, P.T., Schnell, B., and Dickinson, M.H. (2014). Central complex neurons exhibit behaviorally gated responses to visual motion in Drosophila. J. Neurophysiol. 111, 62–71. 3. Ache, J.M., Namiki, S., Lee, A., Branson, K., and Card, G.M. (2019). State-dependent decoupling of sensory and motor circuits underlies behavioral flexibility in Drosophila. Nat. Neurosci. 22, 1132–1139. 4. Ache, J.M., Polsky, J., Alghailani, S., Parekh, R., Breads, P., Peek, M.Y., Bock, D.D., von
Reyn, C.R., and Card, G.M. (2019). Neural basis for looming size and velocity encoding in the Drosophila giant fiber escape pathway. Curr. Biol. 29, 1073–1081.e4.
11. Zhang, Y., Kim, I.-J., Sanes, J.R., and Meister, M. (2012). The most numerous ganglion cell type of the mouse retina is a selective feature detector. Proc. Natl. Acad. Sci. USA 109, E2391–E2398.
5. Namiki, S., Dickinson, M.H., Wong, A.M., Korff, W., and Card, G.M. (2018). The functional organization of descending sensory-motor pathways in Drosophila. Elife 7, e34272.
12. Semmelhack, J.L., Donovan, J.C., Thiele, T.R., Kuehn, E., Laurell, E., and Baier, H. (2014). A dedicated visual pathway for prey detection in larval zebrafish. Elife 3, e04878.
6. Kristan, W.B. (2008). Neuronal decisionmaking circuits. Curr. Biol. 18, R928–R932.
13. Kelesx, M., and Frye, M.A. (2017). Visual behavior: The eyes have it. Elife 6, e24896.
7. von Reyn, C.R., Breads, P., Peek, M.Y., Zheng, G.Z., Williamson, W.R., Yee, A.L., Leonardo, A., and Card, G.M. (2014). A spike-timing mechanism for action selection. Nat. Neurosci. 17, 962–970.
14. Wu, M., Nern, A., Williamson, W.R., Morimoto, M.M., Reiser, M.B., Card, G.M., and Rubin, G.M. (2016). Visual projection neurons in the Drosophila lobula link feature detection to distinct behavioral programs. Elife 5, e21022.
8. Suver, M.P., Mamiya, A., and Dickinson, M.H. (2012). Octopamine neurons mediate flightinduced modulation of visual processing in Drosophila. Curr. Biol. 22, 2294–2302.
15. Mu, L., Ito, K., Bacon, J.P., and Strausfeld, N.J. (2012). Optic glomeruli and their inputs in Drosophila share an organizational ground pattern with the antennal lobes. J. Neurosci. 32, 6061–6071.
9. Zheng, Z., Lauritzen, J.S., Perlman, E., Robinson, C.G., Nichols, M., Milkie, D., Torrens, O., Price, J., Fisher, C.B., Sharifi, N., et al. (2018). A complete electron microscopy volume of the brain of adult Drosophila melanogaster. Cell 174, 730–743.e22.
16. von Reyn, C.R., Nern, A., Williamson, W.R., Breads, P., Wu, M., Namiki, S., and Card, G.M. (2017). Feature integration drives probabilistic behavior in the Drosophila escape response. Neuron 94, 1190–1204.e6.
10. Levick, W.R. (1967). Receptive fields and trigger features of ganglion cells in the visual streak of the rabbits retina. J. Physiol. 188, 285–307.
17. Klapoetke, N.C., Nern, A., Peek, M.Y., Rogers, E.M., Breads, P., Rubin, G.M., Reiser, M.B., and Card, G.M. (2017). Ultra-selective looming detection from radial motion opponency. Nature 551, 237–241.
Gut Homeostasis: Active Migration of Intestinal Epithelial Cells in Tissue Renewal Aglaja Kopf and Michael Sixt* Institute of Science and Technology Austria (IST Austria), am Campus 1, 3400 Klosterneuburg, Austria *Correspondence: [email protected] https://doi.org/10.1016/j.cub.2019.08.068
A new study has uncovered a previously unknown feature of intestinal epithelial cells during gut homeostasis. Biophysical modeling combined with quantitative tissue imaging indicates that epithelial cells actively migrate up the gut villus, challenging the current concept of passive tissue renewal.
The gut is a remarkable organ. Not only is it a selective filter promoting the uptake of dietary nutrients, it also forms a shield against luminal pathogens and has crucial immunoregulatory functions. This requires the combination of two features that appear mutually exclusive: structural barrier function and high absorptive capacity. In order to maximize uptake of nutrients the gut expands its absorptive area by forming finger-like protrusions
(villi) connected to small invaginations into the connective tissue (crypts) (Figure 1A). In this way, the human gut generates a surface area covering more than 30 m2 [1]. This, however, creates fragile structures that are exposed to mechanical, chemical and biological stress and are prone to rapidly disintegrate, causing substantial threats such as systemic infections or inflammatory bowel diseases. To counter
these stresses and to combine tissue integrity with structural resilience, the single-layered intestinal epithelium maintains the highest turnover rates of all organs and renews every three to five days [2]. Rapidly proliferating stem and progenitor cells residing in the wellprotected crypt mature into epithelial cells that are pushed out towards the villus by the proliferation of underlying cells. Thereby only post-mitotic cells are found
Current Biology 29, R1070–R1093, October 21, 2019 ª 2019 Published by Elsevier Ltd. R1091
Dispatches Drosophila Neuroscience: Should I Land or Should I Jump? €dele*, Martha Rimniceanu, and Mark A. Frye Carola Sta Department of Integrative Biology and Physiology, University of California, Los Angeles, CA 90095, USA *Correspondence: [email protected] https://doi.org/10.1016/j.cub.2019.08.039
Information about behavioral states can be integrated in decision-making circuits. In Drosophila, the behavioral state — flying versus not flying — determines whether flies land or jump by dynamically coupling visual information to pre-motor descending neurons. The song ‘‘Should I Stay or Should I Go?’’ by the British punk rock pioneers The Clash is as catchy as its title is timeless. Who cannot relate to the question: Should I do this or should I do that? Every animal, regardless of how many neurons its nervous system is built of, constantly makes choices. But how do animals make choices? Decades of research have shown that the neural mechanisms that lead to decision making are complex and multifactorial. The internal physiological state, such as hunger, external environmental conditions, such as temperature, and the decision maker’s behavioral state, such as locomotion, are important factors in choosing one action over another. The decision whether to keep The Clash tuned in or change the radio station, for example, might depend intrinsically upon your mood or extrinsically upon how often the song gets played on the radio. Furthermore, sensory stimuli alone are often ambiguous if they are not put in context. You may feel the urge to sing to The Clash in the shower, but rather prefer to dance to it in a club. In situations where the sensory stimulus is ambiguous, context is often the key to make the difference between life, death, or reproductive fitness. An approaching predator, for example, can elicit a similar rapidly expanding looming pattern on the observer’s retina as an approaching conspecific. In insects, it has been shown that the decision to avoid or approach an ambiguous object can depend on context-sensitive inputs such as food odor [1], which can be confounded by visual circuits that only function properly during locomotion [2]. Thus, reactions to a single sensory stimulus are unlikely to be hard-wired. However, the neural mechanisms leading
to state-dependent action selection are still nebulous. Two recent studies [3,4] by Jan Ache and Gwyneth Card and their colleagues add to our understanding of where and how in the nervous system information about behavioral state can be integrated into the decision-making chain. In the first study [3], Ache and colleagues demonstrate how Drosophila melanogaster flies integrate behavioral state by dynamically coupling visual input to output pathways to elicit distinct behaviors. In a second study published in Current Biology, Ache and colleagues [4] investigate where in the visual processing networks the coupling to output pathways could occur. When tethered Drosophila are presented with a looming object, Ache and colleagues [3] found that an identical visual looming stimulus can trigger two categorically distinct motor programs — flying flies simultaneously extend all six legs and initiate landing reactions whereas perching flies extend the middle legs and raise their wings to initiate jumping and takeoff. Information about the behavioral state (flying versus perching) can thus be combined with visual input to select the appropriate action (landing versus takeoff) through at least two distinct motor pathways. Ache and colleagues [3] determined where in the neural processing stream the commands for landing and escape are distinguished. In adult Drosophila, 350 pairs of pre-motor ‘descending neurons’ connect the brain to the ventral nerve cord [5], which houses the motor centers that control behavior. Traditionally, descending neurons are viewed as a bottleneck [6], relaying commands from many thousands of brain neurons to only
dozens of central pattern generators in the ventral nerve cord, which then drive combinations of motor neurons to produce coordinated behaviors. The sensorimotor pathway controlling looming-evoked takeoff in Drosophila includes the fast giant-fiber descending neurons [7]. However, the neural circuit that controls landing was unknown. Ache and colleagues [3] found that only two bilaterally symmetric pairs of descending neurons (DNp07 and DNp10) evoke landing-like extension of all six legs when activated optogenetically. Interestingly, the responses to looming visual stimuli of both descending neuron types appeared only when the animals were flying. In tethered non-flying flies, supra-threshold visual responses were abolished in DNp07, while in DNp10 visual responses were strongly attenuated below the threshold required to elicit leg movements. But how exactly is the state of flight communicated to these neurons? One candidate to conditionally link the same sensory input to different behaviors in a state-dependent manner is the biogenic amine octopamine — the invertebrate analog of norepinephrine. On flight initiation, the nervous system of Drosophila is flushed with octopamine which boosts the activity of motionsensitive visual neurons [8]. To determine whether octopamine is involved in conveying flight information to descending neurons, Ache and colleagues [3] applied octopamine to the brains of non-flying Drosophila while they recorded the activity of the descending neurons. After the brain was flushed with octopamine, presenting non-flying flies with a looming stimulus resulted in a flight-like activity pattern in one of the two descending neuron types (DNp07); the
Current Biology 29, R1070–R1093, October 21, 2019 ª 2019 Published by Elsevier Ltd. R1089
Current Biology
Dispatches
State of animal
Flying
Walking/ perching
Sensory stimulus (Looming) Brain
Sensory stimulus (Looming) Brain
Sensory receptors
Sensory receptors
Sensory networks
Sensory networks
? Descending neurons A
Descending neurons B (Decoupled )
CPG A
Motor neurons A
?
Descending neurons A (Decoupled )
Descending neurons B
CPG B
CPG A
CPG B
Motor neurons B
Motor neurons A
Motor neurons B
VNC
VNC
Behavior B (Takeoff )
Behavior A (Landing)
Current Biology
Figure 1. Landing and takeoff decision pathways in Drosophila. A sensory stimulus (in this example a visual looming pattern) activates sensory receptors which then in turn activate sensory networks. The same visual stimulus can recruit several parallel sensory networks, depicted as circles. Each network might contain multiple levels of information processing (not depicted). Processed sensory information leaves the brain and is sent to parallel descending pathways (depicted in blue for landing and in green for takeoff behavior). Depending on the animal’s behavioral state (flying, left; waking/perching, right) sensory information is gated and only transmitted to one descending pathway while the other descending pathway is decoupled (doted rectangles). Question marks indicate that it remains to be tested whether the takeoff pathway in walking/perching flies is gated in a similar way as the landing pathway. Abbreviations: CPG, central pattern generator; VNC, ventral nerve cord.
other DNp10 neurons appeared to be octopamine-insensitive, but are likely to receive direct neuronal feedback from flight motor circuits. This indicates that there are at least two different pathways to relay the same sensory input to motor outputs for two different behavioral actions. Ache and colleagues [3] elegantly demonstrate that landing is not necessarily ‘commanded’ over jumping because of mutual inhibition of descending neurons [6]. Rather, the decision to land is mediated via statedependent gating (Figure 1) of
descending pathways at different sites. One gate operates through the action of octopamine to cut off presynaptic visual input before it reaches the DNp07 descending neurons, whereas the other gate acts through feedback from flight motor centers onto DNp10 themselves. It remains to be tested whether the octopamine-mediated gating takes place at the level of the visual processing networks or at the output of these networks to descending neurons. Currently the visual circuitry that transmits looming information to the landing
R1090 Current Biology 29, R1070–R1093, October 21, 2019
descending neurons is unknown. However, electron microscope reconstruction of the entire Drosophila brain is in progress [9] and it is likely that every component of this circuit will soon be identified. In their second study, Ache and colleagues [4] classify the encoding properties of potential target neurons of the octopamine-mediated gating. Using the well-characterized giant-fiber escape pathway that elicits takeoff in non-flying flies, the authors dissected the wiring logic of how salient visual features of a looming stimulus are encoded by visual projection neurons. Object recognition requires discrimination of global motion generated by self-movement from the visual features of an object. Featuredetecting visual projection neurons, such as retinal ganglion cells, have been well described in different taxa [10–12]. In Drosophila, a class of 20 distinct types of visual projection neurons, the lobula columnar (LC) neurons, are proposed to detect different visual features [13,14] and feed into distinct descending pathways [5,15]. The axon terminals of a given LC type condense into ‘optic glomeruli’ within the central brain [14,15]. A looming stimulus contains multiple salient visual features, such as the angular velocity at which the object expands or its angular size. Ache and colleagues [4] confirmed in unprecedented detail that these two features are encoded by two different LC types — LC4 encodes expansion velocity and LPLC2 encodes expansion size. Summation of both features is necessary to reach action potential threshold in the giant fibers to elicit escape responses [16,17]. Using electron microscope reconstruction, the authors further demonstrate that LC4 and LPLC2 are the sole source of direct excitatory input to these important pre-motor descending fibers. The glomeruli of two other classes of visual projection neurons, LPLC3 and LPLC4 [5], show extensive anatomical overlap with the dendrites of the two newly identified landing descending neurons [3]. It remains to be tested whether LPLC3 and LPLC4 directly synapse onto the landing descending neurons and relay information about visual features of looming patterns in a similar fashion to LC4 and LPLC2. It is intriguing, however, to hypothesize that
Current Biology
Dispatches the same type of visual information is transmitted via at least two parallel visual pathways to distinct pre-motor circuits, thereby adding another gate to the circuit. Ache and colleagues [3,4] marvelously demonstrate how multiple neural mechanisms can be combined to achieve state-dependent action selection, and provide a fly’s answer to the enduring question posed by The Clash: ‘‘Should I Stay or Should I Go?’’ REFERENCES 1. Cheng, K.Y., Colbath, R.A., and Frye, M.A. (2019). Olfactory and neuromodulatory signals reverse visual object avoidance to approach in Drosophila. Curr. Biol. 29, 2058–2065.e2. 2. Weir, P.T., Schnell, B., and Dickinson, M.H. (2014). Central complex neurons exhibit behaviorally gated responses to visual motion in Drosophila. J. Neurophysiol. 111, 62–71. 3. Ache, J.M., Namiki, S., Lee, A., Branson, K., and Card, G.M. (2019). State-dependent decoupling of sensory and motor circuits underlies behavioral flexibility in Drosophila. Nat. Neurosci. 22, 1132–1139. 4. Ache, J.M., Polsky, J., Alghailani, S., Parekh, R., Breads, P., Peek, M.Y., Bock, D.D., von
Reyn, C.R., and Card, G.M. (2019). Neural basis for looming size and velocity encoding in the Drosophila giant fiber escape pathway. Curr. Biol. 29, 1073–1081.e4.
11. Zhang, Y., Kim, I.-J., Sanes, J.R., and Meister, M. (2012). The most numerous ganglion cell type of the mouse retina is a selective feature detector. Proc. Natl. Acad. Sci. USA 109, E2391–E2398.
5. Namiki, S., Dickinson, M.H., Wong, A.M., Korff, W., and Card, G.M. (2018). The functional organization of descending sensory-motor pathways in Drosophila. Elife 7, e34272.
12. Semmelhack, J.L., Donovan, J.C., Thiele, T.R., Kuehn, E., Laurell, E., and Baier, H. (2014). A dedicated visual pathway for prey detection in larval zebrafish. Elife 3, e04878.
6. Kristan, W.B. (2008). Neuronal decisionmaking circuits. Curr. Biol. 18, R928–R932.
13. Kelesx, M., and Frye, M.A. (2017). Visual behavior: The eyes have it. Elife 6, e24896.
7. von Reyn, C.R., Breads, P., Peek, M.Y., Zheng, G.Z., Williamson, W.R., Yee, A.L., Leonardo, A., and Card, G.M. (2014). A spike-timing mechanism for action selection. Nat. Neurosci. 17, 962–970.
14. Wu, M., Nern, A., Williamson, W.R., Morimoto, M.M., Reiser, M.B., Card, G.M., and Rubin, G.M. (2016). Visual projection neurons in the Drosophila lobula link feature detection to distinct behavioral programs. Elife 5, e21022.
8. Suver, M.P., Mamiya, A., and Dickinson, M.H. (2012). Octopamine neurons mediate flightinduced modulation of visual processing in Drosophila. Curr. Biol. 22, 2294–2302.
15. Mu, L., Ito, K., Bacon, J.P., and Strausfeld, N.J. (2012). Optic glomeruli and their inputs in Drosophila share an organizational ground pattern with the antennal lobes. J. Neurosci. 32, 6061–6071.
9. Zheng, Z., Lauritzen, J.S., Perlman, E., Robinson, C.G., Nichols, M., Milkie, D., Torrens, O., Price, J., Fisher, C.B., Sharifi, N., et al. (2018). A complete electron microscopy volume of the brain of adult Drosophila melanogaster. Cell 174, 730–743.e22.
16. von Reyn, C.R., Nern, A., Williamson, W.R., Breads, P., Wu, M., Namiki, S., and Card, G.M. (2017). Feature integration drives probabilistic behavior in the Drosophila escape response. Neuron 94, 1190–1204.e6.
10. Levick, W.R. (1967). Receptive fields and trigger features of ganglion cells in the visual streak of the rabbits retina. J. Physiol. 188, 285–307.
17. Klapoetke, N.C., Nern, A., Peek, M.Y., Rogers, E.M., Breads, P., Rubin, G.M., Reiser, M.B., and Card, G.M. (2017). Ultra-selective looming detection from radial motion opponency. Nature 551, 237–241.
Gut Homeostasis: Active Migration of Intestinal Epithelial Cells in Tissue Renewal Aglaja Kopf and Michael Sixt* Institute of Science and Technology Austria (IST Austria), am Campus 1, 3400 Klosterneuburg, Austria *Correspondence: [email protected] https://doi.org/10.1016/j.cub.2019.08.068
A new study has uncovered a previously unknown feature of intestinal epithelial cells during gut homeostasis. Biophysical modeling combined with quantitative tissue imaging indicates that epithelial cells actively migrate up the gut villus, challenging the current concept of passive tissue renewal.
The gut is a remarkable organ. Not only is it a selective filter promoting the uptake of dietary nutrients, it also forms a shield against luminal pathogens and has crucial immunoregulatory functions. This requires the combination of two features that appear mutually exclusive: structural barrier function and high absorptive capacity. In order to maximize uptake of nutrients the gut expands its absorptive area by forming finger-like protrusions
(villi) connected to small invaginations into the connective tissue (crypts) (Figure 1A). In this way, the human gut generates a surface area covering more than 30 m2 [1]. This, however, creates fragile structures that are exposed to mechanical, chemical and biological stress and are prone to rapidly disintegrate, causing substantial threats such as systemic infections or inflammatory bowel diseases. To counter
these stresses and to combine tissue integrity with structural resilience, the single-layered intestinal epithelium maintains the highest turnover rates of all organs and renews every three to five days [2]. Rapidly proliferating stem and progenitor cells residing in the wellprotected crypt mature into epithelial cells that are pushed out towards the villus by the proliferation of underlying cells. Thereby only post-mitotic cells are found
Current Biology 29, R1070–R1093, October 21, 2019 ª 2019 Published by Elsevier Ltd. R1091