Hérnias abdominais e inguinais em pacientes cirróticos: qual é a melhor conduta?

INTRODUÇÃO: Tradicionalmente os procedimentos abdominais eletivos em pacientes cirróticos têm sido amplamente desencorajados graças à elevada morbi-mortalidade consequente às complicações da cirrose, descritas por diversos autores. Outros serviços, em contrapartida, obtiveram resultados distintos, advogando a favor de cirurgia eletiva. MÉTODOS: Uma revisão de artigos utilizando-se a palavras "abdominal wall hernia" e "cirrhotic patients" foi realizada na base de dados PubMed. Dos resultados obtidos, 28 artigos foram considerados para elaboração desta revisão. RESULTADOS: Pôde-se observar que a incidência de hérnias em parede abdominal é relativamente elevada em pacientes cirróticos, sendo que muitas delas têm evolução desfavorável e requerem tratamento cirúrgico específico. Com o advento do sistema de alocação de órgãos baseados no escore de MELD, muitos centros estão repensando suas condutas em situações como esta, dado que muitos dos pacientes em questão encontram-se em lista de espera para transplante hepático. Dessa forma a cirurgia eletiva tem conquistado maior papel no manejo desta condição com intuito de diminuir morbi-mortalidade nesses pacientes. Além disso, a qualidade de vida mostrou-se um importante fator a ser considerado, estando muito prejudicada nesta condição. CONCLUSÃO: Poucos estudos com grandes amostragens foram conduzidos até o momento e não há consenso sobre qual conduta é a mais indicada levando em consideração taxas de morbi-mortalidade.

Horse spleen segmentation technique as large animal model of preclinical trials

The parenchymal distribution of the splenic artery was studied in order to obtain anatomical basis for partial splenectomy. Thirty two spleens were studied, 26 spleens of healthy horses weighing 320 to 450kg, aged 3 to 12 years and 6 spleens of fetus removed from slaughterhouse. The spleens were submitted to arteriography and scintigraphy in order to have their vascular pattern examined and compared to the external aspect of the organ aiming establish anatomo-surgical segments. All radiographs were photographed with a digital camera and the digital images were submitted to a measuring system for comparative analysis of areas of dorsal and ventral anatomo-surgical segments. Anatomical investigations into the angioarchitecture of the equine spleen showed a paucivascular area, which coincides with a thinner external area, allowing the organ to be divided in two anatomo-surgical segments of approximately 50% of the organ each.

Chronic unpredictable mild stress alters an anxiety-related defensive response, Fos immunoreactivity and hippocampal adult neurogenesis

Previous results show that elevated T-maze (ETM) avoidance responses are facilitated by acute restraint. Escape, on the other hand, was unaltered. To examine if the magnitude of the stressor is an important factor influencing these results, we investigated the effects of unpredictable chronic mild stress (UCMS) on ETM avoidance and escape measurements. Analysis of Fos protein immunoreactivity (Fos-ir) was used to map areas activated by stress exposure in response to ETM avoidance and escape performance. Additionally, the effects of the UCMS protocol on the number of cells expressing the marker of migrating neuroblasts doublecortin (DCX) in the hippocampus were investigated. Corticosterone serum levels were also measured. Results showed that UCMS facilitates ETM avoidance, not altering escape. In unstressed animals, avoidance performance increases Fos-ir in the cingulate cortex, hippocampus (dentate gyrus) and basomedial amygdala, and escape increases Fos-ir in the dorsolateral periaqueductal gray and locus ceruleus. In stressed animals submitted to ETM avoidance, increases in Fos-ir were observed in the cingulate cortex, ventrolateral septum, hippocampus, hypothalamus, amygdala, dorsal and median raphe nuclei. In stressed animals submitted to ETM escape, increases in Fos-ir were observed in the cingulate cortex, periaqueductal gray and locus ceruleus. Also, UCMS exposure decreased the number of DCX-positive cells in the dorsal and ventral hippocampus and increased corticosterone serum levels. These data suggest that the anxiogenic effects of UCMS are related to the activation of specific neurobiological circuits that modulate anxiety and confirm that this stress protocol activates the hypothalamus-pituitary-adrenal axis and decreases hippocampal adult neurogenesis.

Hypothyroidism in adult male rats alters posttranscriptional mechanisms of luteinizing hormone biosynthesis

BACKGROUND: Studies in men are not consistent regarding the effects of thyroid hormone on the production of gonadotropins. In hypothyroidism consequent to diverse causes, an increase or no change in serum luteinizing hormone (LH) have been reported. The attempt to explain the mechanisms involved in this pathology using rats as an experimental model also seems to repeat this divergence, since hypothyroidism has been shown to induce hypogonadotropic hypogonadism, a hypergonadotropic state, or not to affect the basal levels of LH. Notably, the promoter region of the gene encoding the Lh beta subunit and GnRH (gonadotropin-releasing factor) does not contain a thyroid responsive element. Therefore, we investigated the hypothesis that, in male rats, posttranscriptional mechanisms of LH synthesis are altered in hypothyroidism. We also attempted to determine if hypothyroidism directly affects testicular function in male rats. METHODS: Male Wistar rats, 60 days old, were thyroidectomized or sham-operated. After 20 days, they were decapitated, and the pituitaries were collected and analyzed for Lh mRNA, LH content, poly(A) tail length, and polysome profile. The testes were collected and analyzed for Lh receptor mRNA, LH receptor content, and histology using morphometric analyses. The testis, epididymis, seminal vesicle, and ventral prostate were weighed, and serum concentrations of LH, testosterone, thyrotropin (TSH), and triiodothyronine (T3) were measured. RESULTS: Hypothyroidism was associated, in the pituitary, with an increase in Lh mRNA expression, a reduction in Lh mRNA poly(A) tail length, a reduction in the number of LH transcripts associated with polysomes. Pituitary LH was decreased but serum LH was increased from 102 to 543 pg/mL. Despite this, serum testosterone concentrations were decreased from 1.8 to 0.25 ng/mL. A decreased germinative epithelium height of the testes and a reduced weight of androgen-responsive tissues were observed (ventral prostrate: 74 vs. 23 mg/100 g body weight [BW]; seminal vesicle undrained: 280 vs. 70 mg/100 g BW; and seminal vesicle drained: 190 vs. 60 mg/100 g BW). CONCLUSIONS: Hypothyroidism in adult male rats has dual effects on the pituitary testicular axis. It alters posttranscriptional mechanisms of LH synthesis and probably has a direct effect on testicular function. However, these data suggest the possibility that reduced LH bioactivity may account in part for impaired testicular function.

Estudio comparativo de los efectos madurativos de estimular en decúbito prono una muestra de bebés normales

El objetivo de esta tesis ha sido observar y examinar las repercusiones y consecuencias madurativasde colocar y estimular dos grupos de bebés en la postura de decúbito ventral los nueve primeros meses de vida. La investigación consistió en un estudio comparativo, prospectivo y longitudinal de una muestra respresentativa de 132 bebés normales nacidos en el Hospital universitario materno infantil de Canarias, distribuidos en dos grupos: uno experimental de 35 y otro de control de 97 (repartidos en tres subgrupos de 32, 31 y 34 bebés). Se encontraron significativas diferencias entre los dos grupos tanto en las puntuaciones directas de la tabla Alberta (AIMS), como en las cifras de percentil. Se analizaron como indicadores de cada período, el sostén cefálico a los 3 meses, el volteo a los 6 y el gateo a los 9 meses. Por la importancia que tienen como logros motores de cada etapa, los resultados fueron notorios. Se valoraron también las plagiocegalias posicionales y se constata que hay una relación inversa entre la incidencia de plagiocefalias posicionales y el hábito de poner a los bebés boca abajo desde los primeros meses de vida. De acuerdo a los datos que se derivan de la investigación se puede considerar que estimular boca abajo al lactante despierto, mejora la maduración motora y previene la plagiocefalia posicional.

Diencephalic asymmetries: morphological, immunohistochemical and ultrastructural analysis of habenular nuclei in elasmobranchs and teleosts

The habenular nuclei are diencephalic structures present in Vertebrates and they form, with the associated fiber systems, a part of the system that connects the telencephalon to the ventral mesencephalon (Concha M. L. and Wilson S. W., 2001). In representative species of almost all classes of Vertebrates the habenular nuclei are asymmetric, both in terms of size and of neuronal and neurochemical organization, although different types of asymmetry follow different evolutionary courses. Previous studies have analyzed the spread and diversity of the asymmetry in species for which data are not clear (Kemali M. et al., 1980). Notwithstanding that, it’s still not totally understood the evolution of the phenomenon, and the ontogenetic mechanisms that have led to the habenular asymmetry development are not clear (Smeets W.J. et al., 1983). For the present study 14 species of Elasmobranchs and 15 species of Teleostean have been used. Brains removed from the animals have been fixed using 4% paraformaldehyde in phosphate buffer; brains have been analyzed with different tecniques, and I used histological, immunohistochemical and ultrastructural analysis to describe this asymmetry. My results confirm data previously obtained studying other Elasmobranchs species, in which the left habenula is larger than the right one; the Teleostean show some slightly differences regarding the size of the habenular ganglia, in some species, in which the left habenular nucleus is larger than the right. In the course of studies, a correlation between the habits of life and the diencephalic asymmetry seems to emerge: among the Teleostean analyzed, the species with benthic life (like Lepidorhombus boscii, Platichthys flesus, Solea vulgaris) seem to possess a slight asymmetry, analogous to the one of the Elasmobranchs, while in the other species (like Liza aurata, Anguilla anguilla, Trisopterus minutus) the habenulae are symmetrical. However, various aspects of the neuroanatomical asymmetries of the epithalamus have not been deepened in order to obtain a complete picture of the evolution of this phenomenon, and new searches are needed to examine the species without clear asymmetry, in order to understand the spread and the diversity of the asymmetry among the habenulae between the Vertebrates.

Controllo dell'atto di prensione: coinvolgimento dell'area V6A nell'orientamento del polso

Prehension in an act of coordinated reaching and grasping. The reaching component is concerned with bringing the hand to object to be grasped (transport phase); the grasping component refers to the shaping of the hand according to the object features (grasping phase) (Jeannerod, 1981). Reaching and grasping involve different muscles, proximal and distal muscles respectively, and are controlled by different parietofrontal circuit (Jeannerod et al., 1995): a medial circuit, involving area of superior parietal lobule and dorsal premotor area 6 (PMd) (dorsomedial visual stream), is mainly concerned with reaching; a lateral circuit, involving the inferior parietal lobule and ventral premotor area 6 (PMv) (dorsolateral visual stream), with grasping. Area V6A is located in the caudalmost part of the superior parietal lobule, so it belongs to the dorsomedial visual stream; it contains neurons sensitive to visual stimuli (Galletti et al. 1993, 1996, 1999) as well as cells sensitive to the direction of gaze (Galletti et al. 1995) and cells showing saccade-related activity (Nakamura et al. 1999; Kutz et al. 2003). Area V6A contains also arm-reaching neurons likely involved in the control of the direction of the arm during movements towards objects in the peripersonal space (Galletti et al. 1997; Fattori et al. 2001). The present results confirm this finding and demonstrate that during the reach-to-grasp the V6A neurons are also modulated by the orientation of the wrist. Experiments were approved by the Bioethical Committee of the University of Bologna and were performed in accordance with National laws on care and use of laboratory animals and with the European Communities Council Directive of 24th November 1986 (86/609/EEC), recently revised by the Council of Europe guidelines (Appendix A of Convention ETS 123). Experiments were performed in two awake Macaca fascicularis. Each monkey was trained to sit in a primate chair with the head restrained to perform reaching and grasping arm movements in complete darkness while gazing a small fixation point. The object to be grasped was a handle that could have different orientation. We recorded neural activity from 163 neurons of the anterior parietal sulcus; 116/163 (71%) neurons were modulated by the reach-to-grasp task during the execution of the forward movements toward the target (epoch MOV), 111/163 (68%) during the pulling of the handle (epoch HOLD) and 102/163 during the execution of backward movements (epoch M2) (t_test, p ≤ 0.05). About the 45% of the tested cells turned out to be sensitive to the orientation of the handle (one way ANOVA, p ≤ 0.05). To study how the distal components of the movement, such as the hand preshaping during the reaching of the handle, could influence the neuronal discharge, we compared the neuronal activity during the reaching movements towards the same spatial location in reach-to-point and reach-to-grasp tasks. Both tasks required proximal arm movements; only the reach-to-grasp task required distal movements to orient the wrist and to shape the hand to grasp the handle. The 56% of V6A cells showed significant differences in the neural discharge (one way ANOVA, p ≤ 0.05) between the reach-to-point and the reach-to-grasp tasks during MOV, 54% during HOLD and 52% during M2. These data show that reaching and grasping are processed by the same population of neurons, providing evidence that the coordination of reaching and grasping takes place much earlier than previously thought, i.e., in the parieto-occipital cortex. The data here reported are in agreement with results of lesions to the medial posterior parietal cortex in both monkeys and humans, and with recent imaging data in humans, all of them indicating a functional coupling in the control of reaching and grasping by the medial parietofrontal circuit.

Cognitive and affective processes in social actions and decisions

The question of how we make, and how we should make judgments and decisions has occupied thinkers for many centuries. This thesis has the aim to add new evidences to clarify the brain’s mechanisms for decisions. The cognitive and the emotional processes of social actions and decisions are investigated with the aim to understand which brain areas are mostly involved. Four experimental studies are presented. A specific kind of population is involved in the first study (as well as in study III) concerning patients with lesion of ventromedial prefrontal cortex (vmPFC). This region is collocated in the ventral surface of frontal lobe, and it seems have an important role in social and moral decision in forecasting the negative emotional consequences of choice. In study I, it is examined whether emotions, specifically social emotions subserved by the vmPFC, affect people’s willingness to trust others. In study II is observed how incidental emotions could encourage trusting behaviour, especially when individuals are not aware of emotive stimulation. Study III has the aim to gather a direct psychophysiological evidence, both in healthy and neurologically impaired individuals, that emotions are crucially involved in shaping moral judgment, by preventing moral violations. Study IV explores how the moral meaning of a decision and its subsequent action can modulate the basic component of action such as sense of agency.

Darstellung der Grenze zwischen dem rechten und linken Leberlappen mit 3D-Rekonstruktionen von Spiral-Computertomographien

Zusammenfassung:Hintergrund/Ziel: Die Beschreibung der funktionellen Einteilung der Leber basiert auf dem Schema von Claude de Couinaud. Die Grenze zwischen der rechten und linken Leberhälfte scheint leicht durch die Lage der mittleren Lebervene lokalisierbar. Nach der gängigen Meinung wird diese Grenze nicht durch die Trias aus Pfortader, Arterie und Gallengang überschritten. Es soll untersucht werden, ob die Lage dieser gefäßarmen Zone zwischen den Pfortaderästen benachbarter Segmente von der Lage der Grenzebene durch die mittlere Lebervene abweicht.Methode: Bei 73 Patienten wurden im Rahmen der normalen präoperativen Diagnostik dreiphasige Spiral-CT Untersuchungen durchgeführt. Aus diesen Daten wurden dreidimensionale Rekonstruktionen erzeugt und ausgewertet. Ergebnisse: In der vorliegenden Untersuchung konnte gezeigt werden, dass die mittlere Sektorengrenze unterschiedliche Positionen einnimmt, je nach welchem Gefäßsystem sie bestimmt wird. Die mittlere Sektorengrenze zeigt hierbei einen Unterschied in ihrer Lage von 14,2° im Median. An der ventralen Leberoberfläche liegt die Grenzebene nach der mittleren Lebervene damit rechts lateral der gefäßarmen Zone zwischen den Pfortaderästen.Schlussfolgerung: Der Unterschied der Grenzebenen ist in dreidimensionalen Rekonstruktionen demonstrierbar und findet Anwendung bei der Segmentzuordnung von Läsionen. Diese Rekonstruktionen erleichtern die interdisziplinäre Kommunikation und erlauben eine vereinfachte und möglicherweise präzisere Operationsplanung.

Analyse der temporären Neuroblastenbildung und der segmentalen Spezifizierung des Neuroblasten 6-4 im embryonalen zentralen Nervensystem von Drosophila melanogaster

Die vorliegende Arbeit gewährte neue Einblicke in zwei fundamentale Vorgänge der frühen Neurogenese von Drosophila melanogaster. Der erste Teil untersuchte die zeitliche Spezifizierung der Neuroblastenidentitäten. Durch die Expression verschiedener Gene entlang der Dorsoventral- und der Anterioposteriorachse wird ein kartesisches Koordinatensystem aufgebaut, indem ein Neuroblast (NB), der in einem bestimmten Quadranten entsteht, eine spezifische Identität erhält. Die Delamination der NBs erfolgt in fünf Segregationswellen, wobei in jeder Welle die gleiche Population NBs gebildet wird. In dieser Arbeit konnte nun gezeigt werden, dass es nicht nur einen räumlichen, sondern auch einen zeitlichen Aspekt bei der Entstehung der NBs gibt: So zeigten Transplantationsexperimente, dass sowohl im frühen als auch im späten Neuroektoderm extrinsische induktive Signale an der Spezifizierung der Neuroblastenidentität beteiligt sind. Die Natur dieser Signale bleibt noch unklar. Allerdings stellen die Segmentpolaritätsgene aufgrund ihrer dynamischen Expression eine potenzielle Kandidatengruppe dar. Der zweite Teil beschäftigte sich mit der segmentalen Spezifizierung der Neuroblasten. Für diesen Prozess zeigten frühere Genexpressionsstudien, dass NBs, die zwar an korrespondierenden Positionen innerhalb des kartesischen Systems, aber in unterschiedlichen Segmenten gebildet werden, die gleichen Genexpressionsmuster aufweisen und fast identische Zellstammbäume hervorbringen. Einige dieser seriell homologen NBs generieren jedoch segmentspezifische Zellstammbäume – ein solches Beispiel ist der NB6-4, der als Modellsystem benutzt wurde. Für die thorakale Variante dieses NBs konnte ich zeigen, dass die Homöotischen Gene zur Spezifizierung nicht notwendig sind – thorakales Schicksal ist eine Grundidentität. Diese wird in abdominalen Segmenten jedoch durch die Funktion der Homöotischen Gene abdominal-A (abd-A) und Abdominal-B (Abd-B) in abdominales Schicksal transformiert. Dieser segmentale Unterschied wird durch die Regulation des Zellzyklusgens CycE bewerkstelligen. Genauer: CycE ist notwendig, um neurogliales Schicksal in thorakalen Segmenten zu generieren und ausreichend, dieses Schicksal ebenfalls in abdominalen Segmenten zu erzeugen. Eine direkte Inhibierung der Expression von CycE durch Abd-A in abdominalen Segmenten führt dagegen zu einer differenziellen Expression von CycE im neuronalen thorakalen Anteil des Zellstammbaums. Weiterhin konnten in einem Enhancerelement, das für die Expression von CycE im Nervensystem verantwortlich ist, mehrere Bindestellen für Abd-A und Abd-B gefunden werden. Die gewonnen Daten legen – in Verbindung mit bereits bekannten Ergebnissen – den Schluss nahe, dass diese neuronspezifizierende Funktion von CycE unabhängig von seiner Rolle im Zellzyklus ist.

Jaw mechanics of the pterosaur skull construction and the evolution of toothlessness

In the present study, pterosaur skull constructions were analysed using a combined approach of finite element analysis (FEA), static investigations as well as applying classical beam theory and lever mechanics. The study concentrates on the operating regime „bite“, where loads are distributed via the dentition or a keratinous rhamphotheca into the skull during jaw occlusion. As a first step, pterosaur tooth constructions were analysed. The different morphologies of the tooth construction determine specific operational ranges, in which the teeth perform best (= greatest resistance against failure). The incomplete enamel-covering of the pterosaur tooth constructions thereby leads to a reduction of strain and stress and to a greater lateral elasticity than for a complete enamel cover. This permits the development of high and lateral compressed tooth constructions. Further stress-absorption occurs in the periodontal membrane, although its mechanical properties can not be clarified unambiguously. A three-dimensionally preserved skull of Anhanguera was chosen as a case-study for the investigation of the skull constructions. CT-scans were made to get information about the internal architecture, supplemented by thin-sections of a rostrum of a second Anhanguera specimen. These showed that the rostrum can be approximated as a double-walled triangular tube with a large central vacuity and an average wall-thickness of the bony layers of about 1 mm. On base of the CT-scans, a stereolithography of the skull of Anhanguera was made on which the jaw adductor and abductor muscles were modelled, permitting to determine muscular forces. The values were used for the lever mechanics, cantilever and space frame analysis. These studies and the FEA show, that the jaw reaction forces are critical for the stability of the skull construction. The large jugal area ventral to the orbita and the inclined occipital region act as buttresses against these loads. In contrast to the orbitotemporal region which is subject to varying loading conditions, the pattern in the rostrum is less complex. Here, mainly bending in dorsal direction and torsion occur. The hollow rostrum leads to a reduction of weight of the skull and to a high bending and torsional resistance. Similar to the Anhanguera skull construction, the skulls of those pterosaur taxa were analysed, from which enough skull material is know to permit a reliable reconstruction. Furthermore, FEA were made from five selected taxa. The comparison of the biomechanical behaviour of the different skull constructions results in major transformational processes: elongation of rostra, inclination of the occipital region, variation of tooth morphology, reduction of the dentition and replacement of teeth by a keratinous hook or rhamphotheca, fusion of naris and antorbital fenestra, and the development of bony and soft-tissue crests. These processes are discussed for their biomechanical effects during bite. Certain optional operational ranges for feeding are assigned to the different skull constructions and previous hypotheses (e.g. skimming) are verified. Using the principle of economisation, these processes help to establish irreversible transformations and to define possible evolutionary pathways. The resulting constructional levels and the structural variations within these levels are interpreted in light of a greater feeding efficiency and reduction of bony mass combined with an increased stability against the various loads. The biomechanical conclusive pathways are used for comparison and verification of recent hypothesis of the phylogenetic systematics of pterosaurs.

Untersuchungen zur Funktion und Regulation der Rezeptor-Tyrosin-Phosphatase RPTPlambda bei der Entwicklung des Mittel- und Hinterhirns

Der isthmische Organisator liegt an der Grenze zwischen dem sich entwickelnden Mittel- und Hinterhirn und kontrolliert Wachstum und Musterbildung dieser beiden Hirnregionen. In der vorliegenden Arbeit wird die räumliche und zeitliche Expression der Rezeptor-ähnlichen Protein Tyrosin Phosphatase lambda aus dem Huhn (cRPTPλ, auch als cRPTPψ bekannt) während der Entwicklung dieser Struktur beschrieben. Nach einer anfänglich weitläufigen Expression im kaudalen Vorderhirn und in der Mittelhirnregion, beschränkt sich die Expression von cRPTPλ zwischen dem embryonalen Tag E2 und E3.5 auf die ventrale Mittellinie des Neuralrohrs, den Bereich der späteren neuralen Retina und Linse und auf einen schmalen Ring anterior der isthmischen Einschnürung, welcher der molekularen Mittel- / Hinterhirngrenze (MHO) entspricht. Ab dem embryonalen Tag E3.5 wird RPTPλ dann auch im gesamten Mittelhirn gebildet. Um Hinweise auf die Funktion von cRPTPλ zu bekommen, wurde die Regulation dieses Moleküls untersucht. Die Expression von cRPTPλ am MHO wird von dem Fibroblasten Wachstumsfaktor Fgf8 und dem Transkriptionsfaktor Lmx1b, nicht aber von dem sezernierten Glykoprotein Wnt1 induziert. Der Transkriptionsfaktor En-1 unterdrückt die Expression von cRPTPλ am MHO. cRPTPλ-Expression im Mittelhirn wird negativ durch das sezernierte Protein Sonic Hedgehog reguliert, während Lmx1b und En-1 dort keinen Einfluss auf das Expressionsmuster von cRPTPλ haben. Fgf8 und Wnt1 sind maßgeblich an der Regulation von Wachstum und Musterbildung des embryonalen Mittelhirns beteiligt. Funktionelle Studien zu RPTPλ deuten darauf hin, dass dieses Protein als negativer Rückkopplungsmechanismus beider Signalwege wirken kann. RNAi- und Überexpressionsstudien am MHO lieferten Hinweise darauf, dass RPTPλ der Induktion der Wnt1-Expression durch Fgf8 entgegenwirkt. Dies scheint durch Interaktion noch unbekannter Faktoren mit der Juxtamembrandomäne von RPTPλ vermittelt zu werden. Auf das Expressionsmuster von Fgf8 selbst, oder einer Reihe anderer Faktoren, die ebenfalls von Fgf8 reguliert werden, hat RPTPλ allerdings keinen Einfluss. Des Weiteren konnte in dieser Arbeit gezeigt werden, dass eine „künstliche“ Aufrechterhaltung der Expression von cRPTPλ im Mittelhirn zwischen dem embryonalen Tag E2 und E3.5 zu einem stark verkleinerten Mesenzephalon führt. RPTPλ bindet in vivo an β-Catenin, ein zentrales Protein des kanonischen Wnt-Signalweges, und moduliert dadurch vermutlich das Wnt-Signal, welches seinerseits Proliferation im Mesenzephalon fördert. Durch diesen Mechanismus könnte cRPTPλ als „Bremse“ des kanonischen Wnt-Signalweges im Mittelhirn wirken.