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Jose Ferran
  • Murcia, Murcia, Spain

Jose Ferran

<p><b>(A</b>) Summary of all identified anteroposterior (AP) and dorsoventral (DV) partitions of the neural plate of amphioxus. (<b>B-B′′</b>) Topological comparison of major molecular subdivisions between... more
<p><b>(A</b>) Summary of all identified anteroposterior (AP) and dorsoventral (DV) partitions of the neural plate of amphioxus. (<b>B-B′′</b>) Topological comparison of major molecular subdivisions between cephalochordates and vertebrates. (<b>C,C′</b>) Neural plate model highlighting the basal and alar plates of Rostral-hypothalamo–prethalamic primordium (Rostral-HyPTh) (orange) and the whole floor plate domain (gray) and its correspondence in a late larval stage (adapted from [<a href="http://www.plosbiology.org/article/info:doi/10.1371/journal.pbio.2001573#pbio.2001573.ref090" target="_blank">90</a>]). (<b>C′′</b>) Vertebrate neural tube highlighting the Terminal-Hypothalamic prosomere (orange) and the whole floor plate (grey).</p
A well-documented method and experimental design are essential to ensure the reproducibility and reliability in animal research. Experimental studies using exercise programs in animal models have experienced an exponential increase in the... more
A well-documented method and experimental design are essential to ensure the reproducibility and reliability in animal research. Experimental studies using exercise programs in animal models have experienced an exponential increase in the last decades. Complete reporting of forced wheel and treadmill exercise protocols would help to ensure the reproducibility of training programs. However, forced exercise programs are characterized by a poorly detailed methodology. Also, current guidelines do not cover the minimum data that must be included in published works to reproduce training programs. For this reason, we have carried out a systematic review to determine the reproducibility of training programs and experimental designs of published research in rodents using a forced wheel system. Having determined that most of the studies were not detailed enough to be reproducible, we have suggested guidelines for animal research using FORCED exercise wheels, which could also be applicable to ...
Fish have colonized nearly all aquatic niches, making them an invaluable resource to understand vertebrate adaptation and gene family evolution, including the evolution of complex neural networks and modulatory neurotransmitter pathways.... more
Fish have colonized nearly all aquatic niches, making them an invaluable resource to understand vertebrate adaptation and gene family evolution, including the evolution of complex neural networks and modulatory neurotransmitter pathways. Among ancient regulatory molecules, the gaseous messenger nitric oxide (NO) is involved in a wide range of biological processes. Because of its short half-life, the modulatory capability of NO is strictly related to the local activity of nitric oxide synthases (Nos), enzymes that synthesize NO from L-arginine, making the localization of Nos mRNAs a reliable indirect proxy for the location of NO action domains, targets, and effectors. Within the diversified actinopterygian nos paralogs, nos1 (alias nnos) is ubiquitously present as a single copy gene across the gnathostome lineage, making it an ideal candidate for comparative studies. To investigate variations in the NO system across ray-finned fish phylogeny, we compared nos1 expression patterns duri...
Most of the studies on neurochemical mapping, connectivity, and physiology in the hypothalamic region were carried out in rats and under the columnar morphologic paradigm. According to the columnar model, the entire hypothalamic region... more
Most of the studies on neurochemical mapping, connectivity, and physiology in the hypothalamic region were carried out in rats and under the columnar morphologic paradigm. According to the columnar model, the entire hypothalamic region lies ventrally within the diencephalon, which includes preoptic, anterior, tuberal, and mamillary anteroposterior regions, and sometimes identifying dorsal, intermediate, and ventral hypothalamic partitions. This model is weak in providing little or no experimentally corroborated causal explanation of such subdivisions. In contrast, the modern prosomeric model uses different axial assumptions based on the parallel courses of the brain floor, alar-basal boundary, and brain roof (all causally explained). This model also postulates that the hypothalamus and telencephalon jointly form the secondary prosencephalon, separately from and rostral to the diencephalon proper. The hypothalamus is divided into two neuromeric (transverse) parts called peduncular an...
Neuronal phenotypes are controlled by terminal selector transcription factors in invertebrates, but few examples of such regulators have been provided in vertebrates. TCF7L2 has been identified as a regulator of efferent outgrowth in the... more
Neuronal phenotypes are controlled by terminal selector transcription factors in invertebrates, but few examples of such regulators have been provided in vertebrates. TCF7L2 has been identified as a regulator of efferent outgrowth in the thalamus and habenula. We used a complete and conditional knockout of Tcf7l2 in mice to investigate the hypothesis that TCF7L2 plays a dual role in thalamic neuron differentiation and functions as a terminal selector. Connectivity and cell clustering was disrupted in the thalamo-habenular region in Tcf7l2-/- embryos. The expression of subregional thalamic and habenular transcription factors was lost and region-specific cell migration and axon guidance genes were downregulated. In mice with postnatal Tcf7l2 knockout, the induction of genes that confer terminal electrophysiological features of thalamic neurons was impaired. Many of these genes proved to be TCF7L2 direct targets. The role of TCF7L2 in thalamic terminal selection was functionally confir...
The developing mesencephalic trigeminal nucleus (nucleus of the fifth cranial nerve; Mes5) is composed of four neuron populations: 1) the medial group, located at the tectal commissure; 2) the lateral group distributed along the optic... more
The developing mesencephalic trigeminal nucleus (nucleus of the fifth cranial nerve; Mes5) is composed of four neuron populations: 1) the medial group, located at the tectal commissure; 2) the lateral group distributed along the optic tectum hemispheres; 3) a group outside the neural tube; and 4) a population located at the posterior commissure. The present work aims to elucidate the site of appearance, temporal evolution, and spatial distribution of the four Mes5 populations during development. According to detailed qualitative observations Mes5 neurons appear as a primitive unique population along a thin dorsal medial band of the mesencephalon. According to quantitative analyses (changes in cell density along defined reference axes performed as a function of time and space), the definitive spatial pattern of Mes5 neurons results from a process of differential cell movements along the tangential plane of the tectal hemispheres. Radial migration does not have a relevant developmental role. Segregation of medial and lateral group populations depends on the intensity of the lateral displacements. The mesenchymal population appears as an outsider subset of neurons that migrate from the cephalic third of the neural tube dorsal midregion to the mesenchymal compartment. This process, together with the intensive lateral displacements that the insider subset undergoes, contributes to the disappearance of this transient population. We cannot find evidence indicating that neural crest-derived precursors enter the neural tube and differentiate into Mes5 neurons. Our results can be better interpreted in terms of the notion that a dorsal neural tube progenitor cell population behaves as precursor of both migrating peripheral descendants (neural crest) and intrinsic neurons (Mes5).
La pandemia actual por la Covid-19 y su consecuente distanciamiento social ha acelerado la transformación de la educación tradicional hacia la educación en línea. Sin embargo, esta transformación se ha adaptado a nivel tecnológico, pero... more
La pandemia actual por la Covid-19 y su consecuente distanciamiento social ha acelerado la transformación de la educación tradicional hacia la educación en línea. Sin embargo, esta transformación se ha adaptado a nivel tecnológico, pero no pedagógico. El objetivo de este estudio ha sido analizar la adquisición de conocimientos anatómicos de los estudiantes de CAFD mediante el uso de vídeos e imágenes estáticas de surf gestionadas a través de un blog. Un total de 106 estudiantes del grado de CAFD participaron en el presente trabajo. Para el análisis del efecto en el aprendizaje se ha realizado un examen que contenía cinco preguntas sobre la anatomía aplicada al surf tras la visualización de los vídeos/imágenes. Tras el análisis estadístico, se observó un porcentaje de aciertos de 66.0%, 51.9%, 62.3% y 63.2%, para las preguntas 1, 2, 4 y 5 respectivamente. Esta metodología basada esencialmente en un análisis del movimiento permite una comprensión funcional de la anatomía del aparato l...
This essay re-examines the singular case of the supposedly unique rostrally elongated notochord described classically in amphioxus. We start from our previous observations in hpf 21 larvae [Albuixech-Crespo et al., 2017] indicating that... more
This essay re-examines the singular case of the supposedly unique rostrally elongated notochord described classically in amphioxus. We start from our previous observations in hpf 21 larvae [Albuixech-Crespo et al., 2017] indicating that the brain vesicle has rostrally a rather standard hypothalamic molecular configuration. This correlates with the notochord across a possible rostromedian acroterminal hypothalamic domain . The notochord shows some molecular differences that specifically characterize its pre-acroterminal extension beyond its normal rostral end under the mamillary region. We explored an alternative interpretation that the putative extension of this notochord actually represents a variant form of the prechordal plate in amphioxus, some of whose cells would adopt the notochordal typology, but would lack notochordal patterning properties, and might have some (but not all) prechordal ones instead. We survey in detail the classic and recent literature on gastrulation, prech...
El uso de las tecnologías de la información y la comunicación permite crear recursos didácticos que facilitan el aprendizaje fundamentalmente por su efecto motivacional. El objetivo del estudio ha sido analizar el uso de videos y de... more
El uso de las tecnologías de la información y la comunicación permite crear recursos didácticos que facilitan el aprendizaje fundamentalmente por su efecto motivacional. El objetivo del estudio ha sido analizar el uso de videos y de imágenes estáticas de escalada, en el proceso de enseñanza-aprendizaje del aparato locomotor en la asignatura anatomía funcional en Ciencias de la Actividad Física y del Deporte (CAFD). Un total de 106 estudiantes del Grado de CAFD completaron el presente trabajo. Para el análisis del efecto en el aprendizaje se ha realizado un examen que contenía cinco preguntas sobre la anatomía aplicada a la escalada tras la visualización de los vídeos/imágenes. Tras el análisis estadístico, se observó un porcentaje de aciertos de 66,9% y 69,2 % en las preguntas 1 y 3 respectivamente, mientras que en las preguntas 2, 4 y 5 se observó un porcentaje de aciertos inferior. Esta metodología permite un análisis del movimiento ligado a una comprensión directa del aparato loc...
Determining the body composition during adolescence can predict diseases such as obesity, diabetes, and metabolic syndromes later in life; and physical activity became an effective way to restore changes in body composition. However,... more
Determining the body composition during adolescence can predict diseases such as obesity, diabetes, and metabolic syndromes later in life; and physical activity became an effective way to restore changes in body composition. However, current available literature assessing the body composition before, during and after adolescence in female and male rodents by in vivo techniques is scarce. Thus, by using computerized tomography, we aimed to define the baseline of the weight and body composition during the adolescence and young adulthood of female and male Sprague–Dawley rats (on P30, P60 and P90) under standard diet. Then, we determined the effect of 18 days of forced exercise on the body weight and composition during the early adolescence (P27-45). The highest percentual increments in weight, body volume and relative adipose contents occurred during the female and male adolescence. Forced running during the early adolescence decreased weight, body volume and relative adipose delta an...
Improving exercise capacity during adolescence impacts positively on cognitive and motor functions. However, the neural mechanisms contributing to enhance physical performance during this sensitive period remain poorly understood. Such... more
Improving exercise capacity during adolescence impacts positively on cognitive and motor functions. However, the neural mechanisms contributing to enhance physical performance during this sensitive period remain poorly understood. Such knowledge could help to optimize exercise programs and promote a healthy physical and cognitive development in youth athletes. The central dopamine system is of great interest because of its role in regulating motor behavior through the activation of D1 and D2 receptors. Thus, the aim of the present study is to determine whether D1 or D2 receptor signaling contributes to modulate the exercise capacity during adolescence and if this modulation takes place through the striatum. To test this, we used a rodent model of forced running wheel that we implemented recently to assess the exercise capacity. Briefly, rats were exposed to an 8-day period of habituation in the running wheel before assessing their locomotor performance in response to an incremental ...
Our previous analysis of progenitor domains in the pretectum of Xenopus revealed three molecularly distinct anteroposterior subdivisions, identified as precommissural (PcP), juxtacommissural (JcP), and commissural (CoP) histogenetic... more
Our previous analysis of progenitor domains in the pretectum of Xenopus revealed three molecularly distinct anteroposterior subdivisions, identified as precommissural (PcP), juxtacommissural (JcP), and commissural (CoP) histogenetic domains (Morona et al. [2011] J Comp Neurol 519:1024-1050). Here we analyzed at later developmental stages the nuclei derived from these areas, attending to their gene expression patterns and histogenesis. Transcription-factor gene markers were used to selectively map derivatives of each domain: Pax7 and Pax6 (CoP); Foxp1 and Six3 (JcP); and Xiro1, VGlut2, Ebf1, and Ebf3 (PcP). Additional genoarchitectural information was provided by the expression of Gbx2, NPY, Lhx1, and Lhx9. This allowed both unambiguous characterization of the anuran pretectal nuclei with regard to their origin in the three early anteroposterior progenitor domains, and their comparison with counterparts in the chick and mouse pretectum. Our observations demonstrated a molecular conse...
ABSTRACT This chapter is devoted to explain how to handle with brain specimens to get cryostat, paraffin, or floating vibratome sections and the way they are processed during ISH and IHC. The procedure to be selected is related to the... more
ABSTRACT This chapter is devoted to explain how to handle with brain specimens to get cryostat, paraffin, or floating vibratome sections and the way they are processed during ISH and IHC. The procedure to be selected is related to the study aim, general and rapid mapping, or detailed and high resolution analysis. We likewise place emphasis on how to block (embed) and prepare the tissue blocks for sectioning, insuring that optimal section planes are obtained.
ABSTRACT The diencephalon is one of the three major parts of the forebrain, the other two being the telencephalon and the hypothalamus. It is continuous caudally with the midbrain, and rostrally with the hypothalamus. The developing... more
ABSTRACT The diencephalon is one of the three major parts of the forebrain, the other two being the telencephalon and the hypothalamus. It is continuous caudally with the midbrain, and rostrally with the hypothalamus. The developing diencephalon is formed by three segmental units that are clearly defined by gene expression. The three segments of the diencephalon are called prosomere 3, prosomere 2, and prosomere 1, from rostral to caudal. Each of the three prosomeres has alar and basal components, of which the alar parts are most prominent. The alar regions of the three prosomeres are the prethalamus, thalamus, and pretectum respectively; the smaller basal components form an underlying tegmental region in each case. These tegmental components were previously thought to be part of the midbrain. The alar diencephalic region that separates the midbrain from the thalamus has in the past been loosely referred to as the pretectum, a group of nuclei clustered around the posterior commissure. The neuromeric nature of prosomere 1 is difficult to appreciate in adult brains, because of the morphogenetic deformation of its derived structures between the midbrain on one hand, and prosomere 2 structures on the other. The thalamus is the largest part of the diencephalon in mammals. The two halves of the thalamus are partly fused together across the line of the median third ventricle. All sensory pathways, except the olfactory pathway, end in specific nuclei of the thalamus, and each sensory recipient nucleus projects to a specific area of cortex. The embryonic prosomere 3 of the diencephalon gives rise to the nuclei of the prethalamus. The nuclei of the prethalamus form a continuous shell around the rostral, lateral, and ventral topographic margins of the thalamus.
We are interested in stable gene network activities operating sequentially during inner ear specification. The implementation of this patterning process is a key event in the generation of functional subdivisions of the otic vesicle... more
We are interested in stable gene network activities operating sequentially during inner ear specification. The implementation of this patterning process is a key event in the generation of functional subdivisions of the otic vesicle during early embryonic development. The vertebrate inner ear is a complex sensory structure that is a good model system for characterization of developmental mechanisms controlling patterning and specification. Meis genes, belonging to the TALE family, encode homodomain-containing transcription factors remarkably conserved during evolution, which play a role in normal and neoplastic development. To gain understanding of the possible role of homeobox Meis genes in the developing chick inner ear, we comprehensively analyzed their spatiotemporal expression patterns from early otic specification stages onwards. In the invaginating otic placode, Meis1/2 transcripts were observed in the borders of the otic cup, being absent in the portion of otic epithelium closest to the hindbrain. As development proceeds, Meis1 and Meis2 expressions became restricted to the dorsomedial otic epithelium. Both genes were strongly expressed in the entire presumptive domain of the semicircular canals, and more weakly in all associated cristae. The endolymphatic apparatus was labeled in part by Meis1/2. Meis1 was also expressed in the lateral wall of the growing cochlear duct, while Meis2 expression was detected in a few cells of the developing acoustic-vestibular ganglion. Our results suggest a possible role of Meis assigning regional identity in the morphogenesis, patterning, and specification of the developing inner ear.
Members of the Meis family of TALE homeobox transcription factors are involved in many processes of vertebrate development and morphogenesis, showing extremely complex transcriptional and spatiotemporal expression patterns. In this work,... more
Members of the Meis family of TALE homeobox transcription factors are involved in many processes of vertebrate development and morphogenesis, showing extremely complex transcriptional and spatiotemporal expression patterns. In this work, we performed a comprehensive study of chicken Meis genes using multiple approaches. First, we assessed whether the chicken genome contains a Meis3 ortholog or harbors only two Meis genes; we gathered several lines of evidence pointing to a specific loss of the Meis3 ortholog in an early ancestor of birds. Next, we studied the transcriptional diversity generated from chicken Meis genes through alternative splicing during development. Finally, we performed a detailed analysis of chick Meis1/2 expression patterns during early embryogenesis and organogenesis. We show that the expression of both Meis genes begins at the gastrulation stage in the three embryonic layers, presenting highly dynamic patterns with overlapping as well as distinct expression domains throughout development.
We are interested in stable gene network activities operating sequentially during inner ear specification. The implementation of this patterning process is a key event in the generation of functional subdivisions of the otic vesicle... more
We are interested in stable gene network activities operating sequentially during inner ear specification. The implementation of this patterning process is a key event in the generation of functional subdivisions of the otic vesicle during early embryonic development. The vertebrate inner ear is a complex sensory structure that is a good model system for characterization of developmental mechanisms controlling patterning and specification. Meis genes, belonging to the TALE family, encode homodomain-containing transcription factors remarkably conserved during evolution, which play a role in normal and neoplastic development. To gain understanding of the possible role of homeobox Meis genes in the developing chick inner ear, we comprehensively analyzed their spatiotemporal expression patterns from early otic specification stages onwards. In the invaginating otic placode, Meis1/2 transcripts were observed in the borders of the otic cup, being absent in the portion of otic epithelium closest to the hindbrain. As development proceeds, Meis1 and Meis2 expressions became restricted to the dorsomedial otic epithelium. Both genes were strongly expressed in the entire presumptive domain of the semicircular canals, and more weakly in all associated cristae. The endolymphatic apparatus was labeled in part by Meis1/2. Meis1 was also expressed in the lateral wall of the growing cochlear duct, while Meis2 expression was detected in a few cells of the developing acoustic-vestibular ganglion. Our results suggest a possible role of Meis assigning regional identity in the morphogenesis, patterning, and specification of the developing inner ear.
Members of the Meis family of TALE homeobox transcription factors are involved in many processes of vertebrate development and morphogenesis, showing extremely complex transcriptional and spatiotemporal expression patterns. In this work,... more
Members of the Meis family of TALE homeobox transcription factors are involved in many processes of vertebrate development and morphogenesis, showing extremely complex transcriptional and spatiotemporal expression patterns. In this work, we performed a comprehensive study of chicken Meis genes using multiple approaches. First, we assessed whether the chicken genome contains a Meis3 ortholog or harbors only two Meis genes; we gathered several lines of evidence pointing to a specific loss of the Meis3 ortholog in an early ancestor of birds. Next, we studied the transcriptional diversity generated from chicken Meis genes through alternative splicing during development. Finally, we performed a detailed analysis of chick Meis1/2 expression patterns during early embryogenesis and organogenesis. We show that the expression of both Meis genes begins at the gastrulation stage in the three embryonic layers, presenting highly dynamic patterns with overlapping as well as distinct expression domains throughout development.
The developing mesencephalic trigeminal nucleus (nucleus of the fifth cranial nerve; Mes5) is composed of four neuron populations: 1) the medial group, located at the tectal commissure; 2) the lateral group distributed along the optic... more
The developing mesencephalic trigeminal nucleus (nucleus of the fifth cranial nerve; Mes5) is composed of four neuron populations: 1) the medial group, located at the tectal commissure; 2) the lateral group distributed along the optic tectum hemispheres; 3) a group outside the neural tube; and 4) a population located at the posterior commissure. The present work aims to elucidate the site of appearance, temporal evolution, and spatial distribution of the four Mes5 populations during development. According to detailed qualitative observations Mes5 neurons appear as a primitive unique population along a thin dorsal medial band of the mesencephalon. According to quantitative analyses (changes in cell density along defined reference axes performed as a function of time and space), the definitive spatial pattern of Mes5 neurons results from a process of differential cell movements along the tangential plane of the tectal hemispheres. Radial migration does not have a relevant developmental role. Segregation of medial and lateral group populations depends on the intensity of the lateral displacements. The mesenchymal population appears as an outsider subset of neurons that migrate from the cephalic third of the neural tube dorsal midregion to the mesenchymal compartment. This process, together with the intensive lateral displacements that the insider subset undergoes, contributes to the disappearance of this transient population. We cannot find evidence indicating that neural crest-derived precursors enter the neural tube and differentiate into Mes5 neurons. Our results can be better interpreted in terms of the notion that a dorsal neural tube progenitor cell population behaves as precursor of both migrating peripheral descendants (neural crest) and intrinsic neurons (Mes5).
Plasminogen activators are serine proteases which play a key role in morphogenesis and tissue remodelling. Two different molecular types, tissue-type and urokinase-type, were identified and they were postulated to play a role in neural... more
Plasminogen activators are serine proteases which play a key role in morphogenesis and tissue remodelling. Two different molecular types, tissue-type and urokinase-type, were identified and they were postulated to play a role in neural development. The developing chick optic lobe plays a central role in processing visual information. In previous studies we demonstrated the occurrence of high levels of plasminogen activator activity in this model. The aim of the present paper is to study the temporal pattern of expression of this activity and characterize the type of plasminogen activator expressed in the developing optic lobe. Using soluble fractions derived by ultracentrifugation from Triton X-100-treated membrane fractions we measured the protease activity with a radial fibrinolytic assay. Employing different inhibitors of fibrinolytic activity and a zymographic assay, we showed that the developing optic lobe expresses only one type of plasminogen activator which corresponds to an urokinase-type of 70 kDa. Our results indicate that peaks of protease activity temporally correlate with massive neuronal migration, neurite outgrowth and synapse formation and maturation. This suggests that a plasminogen activator could play a role in these developmental events. This consistent pattern of variability strongly suggests that it is developmentally regulated and, if so, it could be a reliable parameter to study neural plastic changes induced by modifications in the environmental stimulation.
The chick retinotectal system is a suitable model to investigate the mechanisms involved in the establishment of synaptic connections in whose refinement nitric oxide was implicated. The purpose of this work was to describe the... more
The chick retinotectal system is a suitable model to investigate the mechanisms involved in the establishment of synaptic connections in whose refinement nitric oxide was implicated. The purpose of this work was to describe the developmental pattern of the nitric oxide synthase (NOS)-positive neurons as well as to determine if it is sensitive to changes in visual stimulation. The NADPH-diaphorase histochemical method was used to describe and quantify NOS neurons in normally stimulated and subnormally stimulated chickens. Nine types of NOS neurons were identified; seven of them express NOS until adulthood, while two of them show only a transient expression. The developmental pattern of NOS neurons follows the process of laminar segregation. It can be divided into three phases. The first includes the onset of NOS expression in periventricular neurons and the formation of a deep network of NOS fibers during early development. These neurons do not show any significant change in subnormally stimulated animals. The second phase includes the appearance of two transient NOS populations of bipolar neurons that occupy the intermediate layers during the optic fibers ingrowth. One of them significantly changes in subnormally stimulated chicks. The third phase occurs when the transitory expression of bipolar neurons decreases. It includes NOS expression in six neuronal populations that innervate the superficial retinorecipient layers. Most of these cells suffer plastic changes in subnormally stimulated chicks. The diversity of neuronal types with regard to their morphology, location, and sensitivity to visual stimulation strongly suggests that they serve different functions. J. Comp. Neurol. 494:1007–1030, 2006. © 2005 Wiley-Liss, Inc.
Plasminogen activators play key roles in several developmental events. In previous works we demonstrated the existence of typical developmental patterns of protease activity in the chick optic lobe and cerebellum. The aim of this work is... more
Plasminogen activators play key roles in several developmental events. In previous works we demonstrated the existence of typical developmental patterns of protease activity in the chick optic lobe and cerebellum. The aim of this work is to study the temporal pattern of development of plasminogen activator activity in the brain hemispheres. Plasminogen activator activity was assayed in soluble fractions derived by ultracentrifugation from Triton X-100 treated membrane fractions by using a radial fibrinolytic assay. Employing different inhibitors and anti-plasminogen activators antibodies we showed that developing brain hemispheres express only one type of enzyme which corresponds to the urokinase-type. Other results indicate that the protease activity displays a temporal pattern which completely differs from those of general parameters of development. This suggests that the plasminogen activator activity is developmentally regulated and could display specific functions during particular stages of development.

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