b2st kikwang dating The riding that Viggo Mortensen did was awesome and the horse that was Hidalgo was quite an actor. I was riveted throughout and it should be considered an epic. This movie shows so much about this particular piece of our past and how we started and what happened to the Native American Indians and to the Mustangs. We don't have enough of this kind of movie now. There are children that don't know about these things. There were many messages in this movie that were courageously and sensitively put forth. Viggo Mortensen was perfect in every way as was the horse.
I found all of the actors wonderful, the scenery so different from just a western and the horsemanship outstanding. What a movie. I loved it. I will see it again, in the movie theater, and I will buy it when available. I was surprised at just how good it was, as it has received so little attention.
Viggo Mortensen of Lord of the Rings plays Frank Hopkins, a real-life cowboy, although probably much fictionalized in this movie. He is a half-breed, part Native American and part white. In the film's prologue, he works for the cavalry and witnesses the massacre of his people at Wounded Knee. The event scars him and he becomes a lush. For some easy money, he and his horse, Hidalgo, enter Buffalo Bill's roadshow. Hidalgo is so famous that a sheik has sent a servant to invite him to participate in a race across the Arabian desert, which he accepts, it being a better alternative to the humiliating performances.
It's really a classical adventure movie, with princesses and scimitars and sandstorms and swarms of locusts. Omar Sharif co-stars as the sheik. Its nice to see a movie like this made with care. It never gets stupid, and, while it moves quickly, it isn't too fast, either.
The director is Joe Johnston, whom I think is an undervalued filmmaker who specializes in these kinds of enjoyable yarns. He also made October Sky, which I haven't seen, but has been recommended. The film also features good performances from Zuleikha Robinson, soon to be a star, I'm sure, Louise Lombard, and Adam Alexi-Malle, one of my favorite character actors he was the guy who wrote Chubby Rain in the movie Bowfinger.
Aragorngrace3 7 March One of the best movies so far of and that I have ever seen is Hidalgo. I loved it so much. The story was great and the acting and everything. Ever since I was 6 years old now i'm 15 I loved Viggo Mortensen as an actor, poetry writer, etc I think he is incredible at everything he does or at least tries. What I liked about Hidalgo was the bond Frank T. Hopkins had with his horse Hidalgo. I also liked the humor here and there. I think no one else could of played Frank T. Hopkins like Viggo can. This movie is one I will recommend for everyone to see. It is just great.
Hidalgo has also given me a love for horses more than I had before. For any one who loves racing or horses this is the movie for you to see. Actually, "Hidalgo" meets the criteria of a western hybrid. Usually, Hollywood reins in its oaters on the far side of the Mississippi.
However, this offbeat, picturesque dust-raiser with "Rings" trilogy hero Viggo Mortensen and "Lawrence of Arabia's" Omar Sharif doesn't flog sentiment to death like the usual Disney animal epic. Furthermore, the hell-bent-for-leather competition occurs well off the range in another corner of the world. No, "Hidalgo" isn't the first western to blaze a trail overseas. Dawson's "The Stranger and the Gunfighter" More often, Europeans and Asians do the emigrating. In Edward Dmytryk's "Shalako" a buckskin-clad Sean Connery buckled on a six-shooter as a cavalry scout and escorted aristocratic Bridget Bardot on safari through hostile Indian territory, while Terence Young's "Red Sun" teamed up samurai warrior Toshiro Mifune with roguish bandit Charles Bronson to retrieve a stolen ceremonial sword.
Like the aforementioned frontier classics, "Hidalgo" breaks new ground both with its protagonist and setting. Hopkins with his trusty mustang Hidalgo and sets this exciting saga in the distant deserts of the Middle East. Literally, our hero finds himself a fish-out-of-water in the Middle East without a clue about Muslim culture. Indeed, the most despicable character in "Hidalgo" is a Muslim, but the film presents positive images of Muslims, too. Nevertheless, the filmmakers cast a shadow over Arab culture, particularly its intolerance toward women and its rigidly segregated society, with enslaved Africans languishing in chains.
Eventually, Hopkins frees one, a small boy, and enlists him as his water-bearer. An overzealous trooper tries to take a rifle away from a deaf brave. The struggling Indian accidentally fires a shot that triggers the infamous December 28th massacre in Like the disillusioned Tom Cruise hero in "The Last Samurai," our guilt-ridden protagonist holds himself to blame for the senseless slaughter.
Buffalo Bill J. Simmons of "Spider-Man" advertises Hopkins as the best horseman in the world. Not only is Hopkins the only American in the race, he rides the only mustang. Nobody believes Hopkins has a snowball's chance in the Sahara to win. When Hopkins doesn't fall for Lady Davenport's charms, she bribes Riyadh's evil nephew Katib to kill Hidalgo, Hopkins' beloved horse, and set the half-Sioux, half-white wrangler afoot. Had director Joe Johnston devoted the entire movie to the race, "Hidalgo" would only have been half as interesting. Johnston takes time out from the race to stage a bullet-blazing shoot out as Hopkins rescues Jazira from the bad guys "Indiana Jones" style.
The last hour of this marathon minute epic generates white-knuckled suspense as Hopkins nurses his wounded horse back onto the trail and rides like the wind toward the finish with his opponents nose-to-nose with Hidalgo. Most historians classify Hopkins memoirs as tall tales. Pretty much straightforward in its linear narrative development, the story concentrates on Hopkins with interludes with the Sheik's daughter who behaves a lot like "Mulan.
Mortensen evokes memories of iconic cowboy Gary Cooper.
Viggo appears at ease whether he's straddling his painted pony, twirling his rope, or fanning his single-action Colt's revolver, like Robert Redford in the best-known western hybrid "Butch Cassidy and the Sundance Kid" Sharif and Mortensen have several good scenes together as their relationship gradually goes from adversial to amicable. Meanwhile, Silas Carson excels as Katib.
You'll want to cheer when he gets his comeuppance. Veteran lenser Shelly Johnson of "Jurassic Park 3" captures the scenic grandeur of the sprawling Moroccan locales, which convincingly substitute for Arabia, and gives the action a sense of spectacle with his widescreen photography.
Happily, "Hidalgo" is short on giddy-yap and long on giddy-up. Simlady 4 August Reading one of the commentaries about this movie urged me to write one of my own. It does seem to me, today, that a movie needs to be ridiculously full of stunts and action sequences and blood, violence etc to be considered worth while by the rank and file who are watching.
How sad is that? I guess I am in the minority, but I want more to a movie than special effects. I had wanted to see this movie from the start, but was never able to get to the theater, so I got it the minute it came out on DVD. I know it was supposed to be a "True Story" but as is I would doubt it - too Hollywood. But hey, the long and short of it is.
I am so there. Who cares if it did not really happen this way? Anyway, now that I have seen it, I can't say I was disappointed at all. I was raised in a scouting family that was very involved in "Indian Lore" and the chants brought back memories. I think Native American history is complex and interesting, and we can still learn from the mistakes made on both sides. And Native Lore is ingrained in the message this movie had to tell.
EVERY movie lately seems to be overcoming obstacles and winning even when you had no chance. But this was different. Frank T Hopkins was what was then called a "half breed", but he passed as white, and not wanting to deal with his race, he hid it except for speaking the language, which I assumed many white men who were close to the land could do. Although he tried to deny it, his bloodlines brought him back to it time and again. Although being in the race had nothing to do with being a "half breed" on the surface, it was all about it in the end. Hidalgo was an "Indian pony" - a breed that was facing extinction.
The horse was constantly being put down by both the whites and the Arabs. While defending the horse constantly, Hopkins yet shunned his own heritage and culture, and only when he accepted it did he win the race. And yet he should have known it all along, since the horse, the symbol of that heritage, was his most prized friend. I got my back up a little when I read that someone thought the movie was was "moralistic" until they finally got to the action.
Gee, aren't movies supposed to be moralistic? Should we not learn from our entertainment, or is it just mindless slaughter and CGI? It was like, yeah yeah, forget the plot, let's see some action. Action is fine, but I liked all the little coincidences, symbolisms and tie-ins to other characters.
The tie-in to Jazia the sheik's daughter wearing a veil over her head was perfect. They were both less in the eyes of white men, but in reality they were fine for what they were. They just had to accept it. The symbol of the natives, a necklace given to him by a chief friend, became his symbol as well, when his servant mistakenly used it for their flag. In the end it was no mistake at all. Yes, it was the typical Disney underdog wins, but there was something extra to it.
At least to me, and I am not sorry to say I still watch movies for the message, not the phony thrills. A wonderful movie of the horse and it special relationship with the human being. A complex plot interwoven, beautifully, with the simple story of winning a horse race. We shoud all learn from such a movie that to preserve and protect the wild horse, and all wild animals returns such rewards and meaning to us human beings.
The movie is beautifully acted and a wonderful treat is to see Omar Sharif in a supporting role. It is, also, a wholesome story of honest and self-less love and concern for each other. This is a great movie for all ages. It is a must movie for lovers of horses. Viggo Mortensen must be one of the more interesting and least known great actor.
Picked up this movie because the trailer's looked good and was not disappointed. Maybe just a little long, but the movie flows well - the lead character is likable and you care what happens to him and Hidalgo. Strange that they don't flesh out the other racers before the start though.
We were interested in the story and did a little research - the basic facts appear true he did indeed take part in this race although there is a liberal amount of poetic license, of course. Thought Omar Shariff played a very good part and the rest of the cast gave good support. All in all, a good movie to curl up and enjoy with your chosen loved one! As an admirer of wild horses and a female who happens to love westerns it was great to have a movie with those qualities.
Personal - Full name is Rodrigo Andres Hidalgo If you choose glass lenses, smaller frames will produce lighter lenses and add to your comfort. That's the starting point. He'll take on ominous Arab riders and many dangers. I loved it. This will make your dark adaptation time shorter and improve your night vision considerably. Nevertheless, it was a pattern that created a bitter split in the social elite.
Not having to worry about the language or subject matter was awesome just hearing some of the children in the theater comment on things happening on the screen was incredible they were actually watching the movie not up running around. A rooftop sharpshooter cut him down with a single bullet to the brain. Those in the forefront who tried to escape by turning back were driven forward by pressure from those behind. Rebel trod on rebel, dead or alive, but there were thousands more to replace those who fell. A group of Indians, farther away, released a blizzard of stones with slingshots, driving defenders on the granary roof inside.
Hidalgo, having commandeered Royalist barracks, sipped hot chocolate while the battle raged. The few defenders who survived the ensuing bloodbath were stripped and paraded through the streets. At nightfall the sack of the city began, a drunken orgy of rape and looting, lasting well into the next day. Some women escaped by fleeing from rooftop to rooftop, many with infants in their arms.
Mines and costly mining machinery were systematically wrecked, some so extensively that they remained inoperable for years. Horrified by the chaos, Allende denounced Hidalgo publicly for indulging his unruly, rampaging Indian rebels. Hidalgo retorted in front of his men—a slight Allende would not forget. He had had to swallow the grief and bitterness of abandoning his trusted friend to his fate, then set himself to the daunting task of building a military machine capable of destroying Hidalgo. Meanwhile, flushed with victory, Hidalgo led his Indian horde toward Mexico City, many dressed in fine silks and velvets and lugging stolen carpets, wrought-iron window rejas barred grillwork and doors.
Near the end of October, Allende positioned his small army in the mountain pass of Las Cruces, 30 miles west of the city. Magnificent stone mansions and public buildings, shops, the mint, the viceregal palace, 2, coaches and hundreds of richly adorned churches, monasteries, convents and libraries were all waiting to be plundered.
With a horde of 80, at the city gates and only 2, troops to defend them, the people of Mexico City were in a state of panic. At Las Cruces, the Royalist defenders of the city fought furiously. In two days and nights of savage combat, the carnage on both sides was horrible.
Of the 2, Royalists, a mere survivors straggled back to the capital to await the invasion. Then, for some reason which neither Hidalgo nor Allende ever explained to anyone, no invasion followed. Some believe Hidalgo panicked, thinking Calleja—whom he greatly feared and whose whereabouts were unknown—might catch up to him unexpectedly. Valladolid was the cathedral city of Bishop-elect Abad y Quiepo. An increasingly exasperated Allende panicked, and tried to assassinate Hidalgo by poisoning his wine, but the wily priest made his suspicions of Allende known by employing a taster.
The rebels moved on to Guadalajara, with Calleja in hot pursuit. The position was impregnable except by open attack across a grassy plain separating the armies. Spies informed Calleja that the rebels had 6, cavalry, but only muskets, and 5, infantry-archers. Calleja divided his forces into three groups. Calleja positioned himself in the center, poised to support either wing.
At that moment, Royalist artillery fire struck a loaded rebel ammunition wagon. It went up in a stupendous explosion, igniting the dry winter grass of the plain. Panic-stricken Indians scattered in a universal rout. Seizing the fortunes of battle, Calleja stormed the cliffs behind the rebel entrenchment, driving the enemy from the field.
With his sense of military honor outraged, Allende paused long enough in flight to strip Hidalgo of command, and the priest traveled on as his prisoner. The new commander hurried north to cross into the United States, convinced he could get financial aid, arms and diplomatic recognition from President James Madison, and bring 30, Yankee mercenaries back with him to Mexico. But there were rebel officers who bore professional grudges against Allende, believing he had denied them deserved promotions. One former Royalist regimental, a double turncoat, betrayed him. Following a trial, the key conspirators were convicted and sentenced to death by firing squad.
Hidalgo was the last to die. To his final breath he swore he was destined to do exactly what he had done. Calleja became viceroy, but later, embittered and traumatized by the revolt, retired to Spain. Proud Allende, convicted as a traitorous soldier, suffered the indignity of being shot in the back by his executioners.
In order to develop into a functional tissue or organ, both patterning and growth have to be tightly controlled and coordinated. How this regulation is achieved is an extraordinarily complex problem. As is the case with many fundamental mechanisms, also the interplay between growth and patterning has been most widely investigated in Drosophila [ 1 — 4 ]. Pattern formation in the eye disc starts during early third instar with the appearance of the morphogenetic furrow MF , a straight epithelial indentation that runs along the dorsoventral DV axis of the Drosophila eye disc and that emerges at the posterior margin of the disc [ 5 ].
The MF is a moving signaling centre that separates the proliferating anterior to the MF and the differentiating posterior to the MF zones in the disc Fig 1A. As the MF sweeps across the disc from its posterior to its anterior side, undifferentiated proliferating cells cease to proliferate at the MF and start differentiating into retina cells behind it [ 5 ]. The velocity of MF movement thus determines the time for which cells on the anterior side of the disc can proliferate.
In front of the MF progenitor cells proliferate arrow A 1 , while behind the MF cells differentiate and eventually form the ommatidia. Hh is expressed in the posterior margin marked in orange , from where it diffuses into the eye disc A2 , and initiates expression of dpp in the MF A3.
Dpp signals by phosphorylation of Mad to pMad A4. Initially Hth is present throughout the disc. As the Hth levels decline, progenitor cells can transit into MF cells A9. Hh supports the differentiation process by inducing the differentiation of MF cells A The eye primordium is marked with an ellipse in b,c. Same color code as in c. At a molecular level, many signals that are involved in the initiation and progression of the morphogenetic furrow have been described [ 6 ].
Initiation of MF movement requires the production of the diffusible morphogen Hedgehog Hh at the posterior eye disc margin. Furthermore, it is known that both Hh and Dpp signaling lead to the downregulation of the transcription factor homothorax hth [ 7 ]. Behind the MF, the newly differentiated photoreceptor cells express hh and the delayed mutual activating loop between Hh and Dpp is able to set the MF in motion. Recent measurements describe this movement of the MF as linear in time [ 9 ].
However, it remains unclear how the signaling network determines the speed of the MF.
By driving the progression of the MF, the signaling network is indirectly regulating proliferation. In addition to driving MF movement and cell differentiation, Dpp signaling affects growth [ 10 — 12 ]. Recently, it was reported that the gradients of the Dpp signaling targets pMad and hairy scale with the anterior length of the eye disc, and the authors suggested that the relative temporal changes in the concentration of the moving Dpp gradient control the proliferation rate and are therefore responsible for the control of growth and its termination [ 9 ]. However, the authors also note that the growth rate is not altered when the only Dpp signalling mediator mad and its downstream target brk are removed from cells.
In order to explore how the spatio-temporal signaling patterns affect the movement of the MF and impact on eye disc growth we translated the signaling network into a spatio-temporal model Fig 1A. Patterning and growth are intricately linked during eye disc development, and we therefore solved the model on a growing domain.
As in previous models of imaginal disc growth [ 13 ], we modeled the epithelium as an incompressible Newtonian fluid with a source that reflects cell proliferation. In order to parameterize the model we measured two key parameters of the model, the degradation rate of Hth as well as the diffusion coefficient of Hh, by Fluorescent Recovery After Photobleaching FRAP.
We show that our model can reproduce the linear movement and speed of the MF. Our model shows the observed growth termination and can reproduce several mutant phenotypes that influence the speed of the MF. We furthermore analyze the impact of parameter perturbations on the linearity and speed of the MF as well as on the final size of the eye disc. Importantly, the model fails to reproduce the scaling of the Dpp gradient with the anterior length of the tissue, suggesting that there must be additional mechanisms in place to ensure scaling. While many open questions remain, our model serves as an important step towards an integrated model for patterning and growth control during development.
We aimed at developing a parsimonious model for eye disc growth and early patterning and thus sought to keep the regulatory interactions as simple as possible while reproducing the measurements. As components of the model we will consider Hh, Dpp, pMad the active form of Mad which transduces the Dpp signal to the nucleus [ 14 ] , Eya, a gene expressed and required for retinal specification and differentiation [ 15 ] and Hth, a protein that prevents premature differentiation anterior to the MF Fig 1A. Representative confocal sections of similar late third instar eye-antennal discs stained for several proteins that are incorporated in the model are shown from different views in Fig 1B—1D.
We will focus on the differentiation process beginning with the initiation of the morphogenetic furrow MF in larvae during early third instar. In front of the MF, progenitor cells proliferate Fig 1A ; arrow A 1 , while behind the MF cells differentiate and eventually form the ommatidia. The production in the margin is incorporated via the boundary condition for Hh Eq 19 , see Methods.
In order to keep the number of parameters small, we use the simplest function that allows us to fit the data, a linear relationship. We note that also a Hill function would have allowed us to reproduce the observed data. However, this would have introduced two additional parameters. As the expression of eya is also induced by Hh [ 19 ] we incorporated a Hh-dependent term Fig 1A ; A6 and a pMad-dependent production term, such that the presence of either pMad or Hh is sufficient to induce eya expression, i.
We notice that we could also have reproduced the mutant behavior if we substituted the Hh-dependent term by a positive feedback of eya on itself or by a direct link of the photoreceptor cells. We therefore describe Hth production by , such that the presence of either pMad or Hh is sufficient to repress hth expression compare Eq 3. Hth is required to maintain the progenitor population in a proliferative and undifferentiated state Fig 1A ; A9 [ 7 ], while Hh is required for the proper differentiation of cells behind the MF into photoreceptor cells Fig 1A ; A Furthermore, forced maintenance of Hth is known to cause severe delays in MF movement and blocks retinal differentiation [ 22 , 23 ].
Downregulation of hth expression therefore allows MF movement [ 20 , 22 , 23 ]. All extracellular molecules can diffuse within the domain, albeit at different speeds. We therefore formulate the model as advection-reaction-dispersion equations for a component i with concentration c i , diffusion coefficient D i and reaction terms R i. The external velocity field is denoted by u : 1.
The reaction terms R i of the components describe the regulatory interactions based on information from the literature and our own experiments as discussed above, and are given by: 2. We use Hill functions to describe regulatory influences. To describe activating influences of a component i we write 3 and we use to describe inhibitory impacts of c i. K i is the Hill constant which specifies the concentration of c i where half-maximal activity is observed, and the Hill coefficient n i defines the steepness of the response.
The different cell types, i. Finally, we need to define the boundary and initial conditions. Hh is expressed in the margin from where it diffuses into the eye disc. We use zero flux boundary conditions for all other signaling molecules, transcription factors and cell types, i. We use zero initial conditions for Hh, Dpp, pMad, and Eya in the entire eye disc domain; MF initiation happens in response to the influx of Hh at the posterior margin see Methods.
Before the initiation of the MF, hth is expressed in all cells of the eye primordium [ 23 ]. We therefore use the steady state concentration as initial concentration, i. The presence of Hth prevents premature cell differentiation. In summary, the initial conditions are: 8. As previously established, the eye disc can be approximated by a 2D ellipse Fig 1B and 1C [ 24 ]. On long time scales, embryonic tissue can often be described by a viscous fluid [ 25 , 26 ]. This approach has previously been used in simulations of early vertebrate limb development [ 27 ] and, in an extended anisotropic formulation, to Drosophila imaginal disc development [ 13 ].
The Navier-Stokes equation is given as: 9 where u denotes the external velocity field used in Eq 1 , S , from definition above, denotes the local growth rate and PL denotes the "posterior length", i. Different mechanisms could, in principle, give rise to this measured decline [ 24 ]. However, in the absence of a confirmed growth-controlling mechanism, we decided to use the functional relation that most accurately describes the growth dynamics in the Drosophila eye disc [ 24 ] without making any statement about how growth may be regulated mechanistically.
We also assume the same growth rule in both x and y directions. This is in agreement with experimental observations: the growth anisotropy parameter was previously determined as [ 9 ]. In most mathematical models the parametrization is crucial for its capabilities to correctly reflect the modeled phenomena. In our model we have three classes of parameters: Production rates and coefficients of the Hill terms, diffusion coefficients and degradation rates.
As the absolute protein concentrations are unknown, the production rates can be set to arbitrary values and the Hill coefficients must then be adjusted to reproduce the experimentally observed protein gradients and gene expression boundaries. We used quantitative confocal microscopy of stained eye discs to detect the spatio-temporal dynamics of the core proteins pMad, Eya, and Hth. Fig 1B—1D shows representative confocal sections of a late third instar eye-antennal disc.
For profile quantification, z-stacks of disc strips were acquired. A single x,y confocal section of one of these strips is shown Fig 1B and 1C. Fig 1D shows a magnified section of a similar eye disc top and a z-section through that section bottom. The regulatory concentration thresholds could be adjusted such that the model reproduced the shapes of the concentration profiles of pMad, Eya, and Hth S1A—S1C Fig , red lines. In this way, all production rates and Hill coefficients could be determined S1 Table.
With respect to the diffusion coefficients, we note that Hth, Eya, and pMad are intracellular proteins and therefore their diffusion across the tissue is negligible. Regarding Dpp kinetic parameters, there are no experimental measures performed in the eye disc. However, in the wing disc , different groups have measured distinct properties regarding Dpp transport, reporting values for Dpp free extracellular diffusion [ 28 ], effective diffusion coefficient [ 28 , 29 ] and the length of the Dpp gradient [ 29 ]. This Dpp decay rate would correspond to a half-life of 45 min. We note that subsequent measurements showed that the Dpp gradient lengthens over time in the wing disc [ 4 ].
Based on this observation, it has been proposed that the Dpp degradation rate would decline over time [ 4 ]. However, we have since shown that the data can be fully explained with a constant degradation rate if the dynamic pre-steady state nature of the patterning process is taken into account [ 30 ]. While we estimated the Dpp half-life to be longer than 10 hours in the wing imaginal disc [ 30 ], we are here focused on the Dpp removal rate from the extracellular space, and the rate of Dpp internalization is fast.
Three crucial parameters have not been previously measured: the diffusion coefficient and the degradation rate of Hh and the degradation rate of Hth. Since the characteristic length of the Hh gradient has been determined, we focused on measuring the effective Hh diffusion coefficient and the Hth degradation rate.
Both experiments were performed using FRAP and were obtained in the wing disc, as this disc is larger and flatter than the eye disc, thus facilitating the experiments and assuming the same dynamics in both disc types. The degradation rate can be calculated by linearly fitting the time series for the bleach-chase analysis of Hth Fig 2B [ 31 ]. The recovery rate that was obtained on the antenna side Fig 2a'' was within the standard deviation of the recovery rate obtained on the eye side Fig 2a'. This implies that the degradation rate does not differ between these two tissues.
This value is similar to previous measurements for Wg in the wing disc [ 29 ], and Wg and Hh have previously been noticed to bear important similarities in their extracellular transport in the wing disc [ 33 ]. The yellow solid circle shows the ROI selected to perform the photobleaching. The yellow dashed circle shows the photobleaching effective area. Here can be observed the nominal diameter 2 r n between yellow solid lines correspondent to the photobleached ROI and the effective diameter 2 r e , between yellow dashed lines, correspondent to the effective photobleached area.
The grey dashed lines show the half recovery time corresponding to one of the samples used in the experiment. In agreement with previous measurements [ 9 ], the MF progresses linearly with time from the posterior towards the anterior side of the domain Fig 4A. Moreover, the speed of MF progression agrees quantitatively. Here, we note that the experimental measurements report the MF position as the average posterior length at a given time point across the disc, while we monitor the MF position as the maximal posterior length at the dorso-ventral boundary to be able to use the previously determined eye disc growth rate in Eq 9 [ 9 ].
We have previously shown that the experimentally determined speed of 3. The model also reproduces the observed growth dynamics Fig 4B—4D. Thus, our simulations show an initial linear increase of the total area followed by a plateau phase Fig 4B. During the plateau phase the anterior area is barely increasing and finally declines in parallel and at a similar rate as the posterior area is increasing due to the differentiation caused by the progression of the MF Fig 4B—4D.
As a result of this, the MF reaches at some point the anterior end of the eye disc which leads to growth termination due to the exhaustion of anterior progenitors. In our numerical simulations, the nonlinearity and speed of the MF movement measured by the root-mean square error and the slope of a linear fit of the posterior length over time as well as the final eye disc size heavily depend on the choice of parameters. As a result of the increased MF speed, the anterior tissue has less time to proliferate and therefore the final eye disc area is smaller Fig 5E and 5F.
Roberto De Sincity needs a job and he needs one now. After a trip across the street to his barber, Jose Luis, and a suggestion from this good friend that he try. axejibykyp.gq: Hidalgo (Widescreen Edition): Viggo Mortensen, Omar Sharif, Said amazing special effects, and memorable characters make HIDALGO one of . The Arabs appeared like Arabs, not Americans in eye liner & black wigs, thus it.
As a result of the slower MF movement the anterior area has more time to proliferate and therefore the final total area increases Fig 5E and 5F. An increased impact of both Dpp and pMad has generally a smaller effect but nevertheless leads to an increase in the MF speed and in the nonlinearity of the MF movement and to a decrease in the final area Fig 5. In panels a, c, and e, the absolute values for speed, nonlinearity and area of the resulting eye discs are shown whereas in b, d, and f, the same data is shown in relation to the wildtype values. We were therefore interested to see to what extent our eye disc model is able to explain these observed effects.
Mutations that reduce Hh activity in the eye disc result in a severe slowdown or stop of MF progression and eye size reduction [ 17 , 37 — 39 ]. In our simulations, reduction of the Hh production rate indeed results in a decreasing speed and an eventual stop of MF movement Fig 6A. Furthermore we observe that the predicted total area of the eye disc overgrows Fig 6B , because the differentiation rate of the proliferating area caused by the furrow is much smaller. This excess of undifferentiated progenitors do not make into the adult head, as hh mutants show smaller eyes but no abnormal overgrowths.
This suggests that there must be some additional control of the anterior area that is not included in the eye disc model, e. The latter is supported by the observation that there is abundant cell death in hh -mutant discs anterior to the MF [ 16 , 17 ]. Furthermore, it was shown that large hh signaling-mutant clones in the eye disc showed a disrupted organization of photoreceptors towards the center of the clone [ 17 ].
Interestingly, we can see that also in simulations of these clones the Hh concentration in the center is not sufficient to differentiate these cells Fig 6C. It is well known that Hh is required for the initiation of the MF, and removal of hh expression in the margin thus prevents MF initiation and eye formation [ 40 , 41 ]. Complete removal of Hh signaling in the simulations precludes production of Dpp and since hth can no longer be downregulated, no MF starts Fig 6D , zero influx. On the other hand, a small reduction in the Hh influx compared to wild type increases eye size because cells have more time to proliferate before the MF is initiated Fig 6D.
In the case of the simulation representing the hypomorphic hh mutant the MF is clearly slower and eventually stops a , while the total area is overgrowing b. Towards the center of the clone the tissue is not differentiated blue color despite residing within the posterior area colored in orange. In panel e an additional simulation with increased dpp production rate blue line is compared. The MF indicated by orange color shows a retardation in the clone. Similar to the phenotype of discs with hypomorphic hh alleles, eye discs harboring a hypomorphic dpp allele have very small adult eyes dpp blk : — ommatidia develop instead of — in the wild type [ 37 ].
In contrast to this, our simulations predict an overgrowth of the total area Fig 6E , red line.